ArticleLiterature Review

Curcumin and its topical formulations for wound healing applications

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Abstract

Oxidative damage and inflammation have been identified, through clinical and preclinical studies, as the main causes of nonhealing chronic wounds. Reduction of persistent chronic inflammation by application of antioxidant and anti-inflammatory agents such as curcumin has been well studied. However, low aqueous solubility, poor tissue absorption, rapid metabolism and short plasma half-life have made curcumin unsuitable for systemic administration for better wound healing. Recently, various topical formulations of curcumin such as films, fibers, emulsion, hydrogels and different nanoformulations have been developed for targeted delivery of curcumin at wounded sites. In this review, we summarize and discuss different topical formulations of curcumin with emphasis on their wound-healing properties in animal models.

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... The former was chosen primarily as an analytical marker with the ease with which it can be detected, providing a facile route through which the operating characteristics of the proposed smart patch system could be readily determined. Curcumin, in contrast, is recognised as a versatile therapeutic agent possessing antimicrobial and anti-inflammatory properties, and there is an extensive literature base dedicated to its clinical application [21][22][23][24][25][26]. Curcumin has been found to be particularly valuable in wound healing, where it has been demonstrated to accelerate wound closure. ...
... As such, there have been considerable efforts to develop functional materials that can provide a mechanism for its controlled release. This has included complexation with cyclodextrin [21] or encapsulation within various polymer films [21,22], hydrogels [23,24], and nanoparticles [25], with most still relying on passive release once in contact with the wound fluid [26]. More recently, there have been reports of stimulus-responsive release (typically pH) [13][14][15][16], but no approach exists that can precisely modulate the release (i.e., scheduled delivery). ...
... Unfortunately, there are no commercial salt variants of curcumin. There have been numerous attempts to counter the curcumin solubility issue with complexation, with cyclodextrin [21] and cationic chitosan [22,23] being among the more common [26]. A novel approach was, therefore, taken in which a second phase-change material was added to the drug-wax composite: O,O -bis(2-aminopropyl) polypropylene glycol-block-polyethylene glycol-block-polypropylene glycol (AP-PEG). ...
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The combination of paraffin wax and O,O′-bis(2-aminopropyl) polypropylene glycol–block–polyethylene glycol–block–polypropylene glycol was used as a phase-change material (PCM) for the controlled delivery of curcumin. The PCM was combined with a graphene-based heater derived from the laser scribing of polyimide film. This assembly provides a new approach to a smart patch through which release can be electronically controlled, allowing repetitive dosing. Rather than relying on passive diffusion, delivery is induced and terminated through the controlled heating of the PCM with transfer only occurring when the PCM transitions from solid to liquid. The material properties of the device and release characteristics of the strategy under repetitive dosing are critically assessed. The delivery yield of curcumin was found to be 3.5 µg (4.5 µg/cm2) per 3 min thermal cycle.
... (1.11 %)] is a yellow chemical compound isolated from the rhizome Curcuma longa L plant (turmeric), from the Zingiberaceae family, native to Southeast Asia and countries like China and India [59]. Despite being used for centuries in the traditional medicine of these countries, it has recently gained a lot of attention from the scientific community due to its pleiotropic effects, with antioxidant [38], anti-inflammatory [39], hypoglycemic [60], wound healing [61] and antimicrobial properties [40][41][42]. Furthermore, being a safe and low-cost molecule, it has shown promising results in the treatment of several autoimmune, inflammatory, metabolic, neoplastic and infectious diseases [60,62,63]. ...
... Furthermore, being a safe and low-cost molecule, it has shown promising results in the treatment of several autoimmune, inflammatory, metabolic, neoplastic and infectious diseases [60,62,63]. However, its real effectiveness has been questioned, due to its low bioavailability, fast metabolism and short half-life [60][61][62][63] in the body, questions that can be minimized in the studies included in this review, since they all evaluated the action of topically applied CUR in the periodontal pocket. ...
Article
Aim Curcumin (CUR) has been used clinically in several studies as a subgingival irrigant or as a photoantimicrobial in combination with a blue light-emitting diode (LED) in antimicrobial photodynamic therapy (aPDT) adjuvant to scaling and root planing (SRP). The aim of this study was to assess the effectiveness of CUR as an irrigant or as a photoantimicrobial in conjunction with the blue LED in aPDT adjuvant to SRP, compared to SRP as conventional mechanical treatment. Materials and methods Fifteen randomized controlled trials (RCT) were included in a qualitative analysis after researching the databases: PubMed / MEDLINE, SCOPUS, EMBASE, Cochrane Central, Web of Science and Scielo. Manual searches were also performed. Five studies were submitted to quantitative analysis, evaluating periodontal clinical parameters such as probing depth (PD) and clinical attachment level (CAL). Results The obtained results have shown clinical benefits in PD reduction and CAL gains at 3 months with the use of CUR as adjuvant therapy to SRP, both as an irrigant or photoantimicrobial, in comparison with SRP monotherapy. Conclusion Currently, there is evidence that treatment with CUR applied as irrigant or in conjunction with the blue LED as aPDT presents superior clinical results in the short term, for clinical periodontics parameters like as PD reduction and CAL gain, when compared to SRP monotherapy in the non-surgical treatment of periodontitis. However, these results cannot be proven in the long term.
... Lin et al. have been recently reported that the antiviral effects of curcumin with different mechanisms against Enterovirus 71(EV71) In-vitro and In-vivo could be improved by the carbon quantum dots of curcumin [100]. Loczechin et al. also reported this important fact that carbon quantum dots alone were effective against human coronavirus (HCoV) by inhibiting the entry receptor of HCoV-229E [101]. ...
... The advancement between these steps depends on the maturation of mast cells, fibroblasts, ECM, keratinocytes, and macrophages which play a pivotal role in wound healing processes. Due to its hydrophobicity and extensive first-pass metabolism, topical administration of curcumin has been shown to have a greater impact on wound healing than oral administration [99][100].In addition to the above discussed successful clinical trials in mentioned diseases and various other biological activities reported in the literature are further presented in Table 2 along with the route of administration and their outcomes. ...
Article
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Curcumin, an important constituent of turmeric used in the traditional medicinal system has suffered considerable controversy. Classification as pan-assay interference compounds and invalid metabolic panaceas contributed toward its inability as a lead compound. The conclusions were drawn on the basis of various clinical trials that failed to prove the medicinal effect of curcumin. The inclusion of high throughput screening studies also contributed to this entitlement. Still, researchers didn't put an end to explore on cur-cumin probably due to the traditionally accepted role of turmeric in medicines. Extensive investigation on curcumin multiplied enormously and more than 27,000 documents results in Scopus with one click on cur-cumin. It being a pharmacologically significant molecule or "Much Ado about Nothing" will always be debatable. In the present review, we have compiled successful clinical trials with curcumin in several diseased conditions including the results of such clinical trials where the prescribed medicine failed to respond.
... When the skin is injured through physical, chemical, mechanical, and/or thermal damage [8], a spontaneous series of events begin to happen, often called the "cascade of healing," to restore the injured tissues [16], replace the damaged structures and prevent the invasion of microorganisms into the damaged tissues. The healing process is composed of four overlapping phases: Hemostasis, Inflammatory, Proliferative, and Maturation phases [17][18][19]. The healing process is remarkable and complex [16], and it is also hindered by local factors including moisture and infection as well as systemic factors including age and nutritional status. ...
... Moreover, macrophages secrete growth factors and proteins that entice immune cells to the wound to restore the devitalized tissues and efferocytosis. Efferocytosis is the elimination of apoptotic neutrophils before they undergo secondary necrosis by macrophages to limit tissue damage and assist its recovery but a prolonged inflammatory phase may lead to cell destruction and changing composition of the extracellular matrix that delay epithelization [17,18,20]. This phase is often characterized by edema, erythema, heat, and pain. ...
Article
Full-text available
When the skin is injured through physical, chemical, mechanical, and/or thermal damage, a spontaneous series of events start to happen, often called the “cascade of healing,” so as to restore the injured tissues, replace the damaged structures and prevent the invasion of pathogens into the damaged tissues. A number of traditional products are available for wound healing such as gels, creams, ointments, dressings and solutions, which depend mainly on moisture intake so as to help tissue repair, yet they do not provide optimal conditions to permit recovery of the wounds. Nanocarriers play a significant role in wound healing, since they are reported to improve drug delivery into the skin through alternation of pharmacokinetics and biodistribution of drugs, hence they increase bioavailability of drugs. Vesicular systems such as liposomes, niosomes, transfersomes, penetration enhancer containing vesicles (PEVs) and ethosomes are among the carriers proven to enhance the therapeutic action of drugs applied for wound healing. In this review, we summarize and discuss different vesicular systems used for wound healing, their composition, their advantages and disadvantages, their methods of preparation and their mechanisms of skin penetration.
... This good encapsulation efficiency of curcumin can be associated with the highly lipophilic nature of CUR that resulted in the remarkable incorporation of CUR into niosome layers (Zhao et al., 2013). EE has been reported to be directly related to lipid concentrations, where higher lipids will lead to the higher loading of lipophilic CUR (Mohanty and Sahoo, 2017). Similarly, it was shown that EE will increase with the growing amount of cholesterol (Akbari et al., 2020). ...
... In upcoming studies, newer formulations considering different concentrations of cholesterol with Tween 40 and various concentrations of CUR could be hypothesized while the effects of other surfactants could also be evaluated. Moreover, the transdermal penetration potential of these niosomes could be evaluated as CUR has been studied in different topical applications (Mohanty and Sahoo, 2017). ...
Article
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Objective: Application of vesicular drug delivery systems has made major progress in pharmaceutical science and technology. Niosomal drug delivery is potentially efficient to improve the pharmacokinetic and pharmacological properties of many compounds. Curcumin (CUR) has several documented anticancer activities; however, it has a low bioavailability that necessitates the development of efficient delivery systems. Accordingly, different niosomal preparations were prepared and evaluated in the present study to find a suitable delivery system. Materials and methods: Span and Tween 20, 40, 60, and 80 were employed with various concentrations of cholesterol for studying the ability to form curcumin-loaded niosomes. Multiple characterization techniques including visual evaluation, particle size analysis, stability, encapsulation efficiency (EE), and release profile were studied. Cytotoxicity of curcumin niosomes on MCF-7 and 3T3 cell lines was determined using MTT assay. Results: Visual and particle size analysis indicated the formation of seven niosomal formulations in the micron size range, while the formulation consisted of Tween 40/cholesterol (50/50 M%) with 0.05% w/v CUR had an average diameter of 475 nm. The latter formulation was selected and it had EE of 78.5%. The CUR release profile showed 18.7% release over a period of 300 min. The MTT results showed that CUR incorporation significantly increased the cytotoxicity of niosomes and the extent of toxicity was higher in MCF-7 cells. Conclusion: In this study, a simple niosomal formulation was developed for CUR loading with favorable physicochemical properties. The presented niosomal curcumin had also considerable effects in cell toxicity studies, which can be suggested for future anticancer studies.
... The studies have shown that during the proliferation phase, curcumin enhances fibroblast migration, enhances granulation tissue formation, collagen deposition, and re-epithelialization. In the final phase of wound healing, by increasing the production of the transforming growth factor β, curcumin enhances wound contractions and therefore increases fibroblast proliferation [203]. Various topical curcumin formulations such as films, fibres, emulsions, hydrogels, and various nanoformulations have been developed for targeted delivery of curcumin at the wounds [203][204][205]. ...
... In the final phase of wound healing, by increasing the production of the transforming growth factor β, curcumin enhances wound contractions and therefore increases fibroblast proliferation [203]. Various topical curcumin formulations such as films, fibres, emulsions, hydrogels, and various nanoformulations have been developed for targeted delivery of curcumin at the wounds [203][204][205]. Sodium alginate-g-poly(N-isopropylacrylamide), (Alg-pNIPAM), a thermosensitive hydrogel with incorporated curcumin as an in vivo wound dressing was synthesized by Zakerikhoob et al. ...
Article
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Curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-hepta-1,6-diene-3,5-dione) is a natural lipophilic polyphenol that exhibits significant pharmacological effects in vitro and in vivo through various mechanisms of action. Numerous studies have identified and characterised the pharmacokinetic, pharmacodynamic, and clinical properties of curcumin. Curcumin has an anti-inflammatory, antioxidative, antinociceptive, antiparasitic, antimalarial effect, and it is used as a wound-healing agent. However, poor curcumin absorption in the small intestine, fast metabolism, and fast systemic elimination cause poor bioavailability of curcumin in human beings. In order to overcome these problems, a number of curcumin formulations have been developed. The aim of this paper is to provide an overview of recent research in biological and pharmaceutical aspects of curcumin, methods of sample preparation for its isolation (Soxhlet extraction, ultrasound extraction, pressurised fluid extraction, microwave extraction, enzyme-assisted aided extraction), analytical methods (FTIR, NIR, FT-Raman, UV-VIS, NMR, XRD, DSC, TLC, HPLC, HPTLC, LC-MS, UPLC/Q-TOF-MS) for identification and quantification of curcumin in different matrices, and different techniques for developing formulations. The optimal sample preparation and use of an appropriate analytical method will significantly improve the evaluation of formulations and the biological activity of curcumin.
... 60 The anti-inflammatory and free-radical scavenging activity of curcumin occur via reduction of lipid peroxidation and reactive oxygen species (ROS). 61 Curcumin protects the skin from oxidative stress as it regulates lipid peroxidation while its antioxidant effect activates the cytoprotective signaling. Furthermore, curcumin confers some protective activity against hydrogen peroxide in human keratinocytes and fibroblasts. ...
... 62 Additionally, it also suppresses inflammation by reducing the transcription factor protein-1 (AP1) while NF-κB reduces the expression of inflammatory cytokines and modulates the pro-inflammatory gene product expression, as shown in a wound model. 61 In an animal study, the anti-inflammatory effect of chrysin-curcumin-loaded nanofibers accelerates wound healing in male rats by decreasing the gene expression for IL-6, TIMP-1, TIMP-2, MMP-2, and iNOS. 63 During proliferation, curcumin activates the growth factors, produces ECM proteins,and helps in collagen synthesis and migration of fibroblasts which aid wound repair. ...
Article
Full-text available
The skin is the largest organ in the human body, composed of the epidermis and the dermis. It provides protection and acts as a barrier against external menaces like allergens, chemicals, systemic toxicity, and infectious organisms. Skin disorders like cancer, dermatitis, psoriasis, wounds, skin aging, acne, and skin infection occur frequently and can impact human life. According to a growing body of evidence, several studies have reported that natural products have the potential for treating skin disorders. Building on this information, this review provides brief information about the action of the most important in vitro and in vivo research on the use of ten selected natural products in inflammatory, neoplastic, and infectious skin disorders and their mechanisms that have been reported to date. The related studies and articles were searched from several databases, including PubMed, Google, Google Scholar, and ScienceDirect. Ten natural products that have been reported widely on skin disorders were reviewed in this study, with most showing anti-inflammatory, antioxidant, anti-microbial, and anti-cancer effects as the main therapeutic actions. Overall, most of the natural products reported in this review can reduce and suppress inflammatory markers, like tumor necrosis factor-alpha (TNF-α), scavenge reactive oxygen species (ROS), induce cancer cell death through apoptosis, and prevent bacteria, fungal, and virus infections indicating their potentials. This review also highlighted the challenges and opportunities of natural products in transdermal/topical delivery systems and their safety considerations for skin disorders. Our findings indicated that natural products might be a low-cost, well-tolerated, and safe treatment for skin diseases. However, a larger number of clinical trials are required to validate these findings. Natural products in combination with modern drugs, as well as the development of novel delivery mechanisms, represent a very promising area for future drug discovery of these natural leads against skin disorders.
... The anti-infective effects makes curcuma appropriate in the wound-healing. Recent studies on the wound-healing properties of curcuma evidence its ability to increase the granulation tissue formation, collagen deposition, tissue changing structure, and wound reducing, favoring, in this way, the healing process [26][27][28][29][30]. ...
Article
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This study aims to investigate the effect of new natural photosensitizers (PS) (based on oregano essential oil, curcuma extract, and arnica oil) through in vitro cytotoxicity and biological tests in rat-induced periodontal disease, treated with photodynamic therapy (aPDT). The cytotoxicity of PS was performed on human dental pulp mesenchymal stem cells (dMSCs) and human keratinocyte (HaCaT) cell lines. Periodontal disease was induced by ligation of the first mandibular molar of 25 rats, which were divided into 5 groups: control group, periodontitis group, Curcuma and aPDT-treated group, oregano and aPDT-treated group, and aPDT group. The animals were euthanized after 4 weeks of study. Computed tomography imaging has been used to evaluate alveolar bone loss. Hematological and histological evaluation showed a greater magnitude of the inflammatory response and severe destruction of the periodontal ligaments in the untreated group.. For the group with the induced periodontitis and treated with natural photosensitizers, the aPDT improved the results; this therapy could be an important adjuvant treatment. The obtained results of these preliminary studies encourage us to continue the research of periodontitis treated with natural photosensitizers activated by photodynamic therapy.
... The preparation of NEs loaded with CCM was based on a previous study by emulsion phase inversion technique [29]. CCM was chosen as a hydrophobic model drug for its ability to enhance the wound healing process [30,31]. ...
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This work combines natural polymers with nanoemulsions (NEs) to formulate nanocomposites as innovative wound dressing. Spray drying has been used to produce alginate-pectin in situ gelling powders as carriers for NEs loaded with curcumin (CCM), a model antimicrobial drug. The influence of NEs encapsulation in polymer-based microparticles was studied in terms of particle size distribution, morphology, and stability after spray drying. NEs loading did not affect the size of microparticles which was around 3.5 µm, while the shape and surface morphology analyzed using scanning electron microscope (SEM), changed from irregular to spherical. Nanocomposites as dried powders were able to form a gel in less than 5 minutes when in contact with simulated wound fluid (SWF), while the value of moisture transmission of the in situ formed hydrogels allowed to promote good wound transpiration. Moreover, rheologic analyses showed that in situ formed gels loaded with NEs appeared more elastic than blank formulations. The in situ formed gel allowed the prolonged release of CCM-loaded NEs in the wound bed, reaching 100% in 24 hours. Finally, powders cytocompatibility was confirmed by incubation with keratinocyte cells (HaCaT), proving that such nanocomposites can be considered a potential candidate for wound dressings.
... The data obtained confirmed that curcumin acts effectively as an antibacterial compound, and that it is a possible candidate for the development of pharmaceutical formulations with the purpose of treating infections caused by resistant strains of S. aureus. In this respect, studies in the literature have reported the development of topical formulations, using curcumin to obtain anti-inflammatory wound healing effects [66][67][68], so these can serve as a basis for the development of formulations with antibacterial action. ...
Article
Staphylococcus aureus is a commensal bacterium and opportunistic human pathogen that can cause a wide variety of clinical infections. It is recognized for its ability to acquire antimicrobial resistance, so methicillin-resistant Staphylococcus aureus (MRSA) infections are a global healthcare challenge. Therefore, the development of new therapeutic options and alternative therapies for treatment is necessary. Curcumin, a polyphenolic substance found in the rhizome of turmeric longa L, has been shown to have several therapeutic properties, including antimicrobial activity. The objective of the study was to evaluate the in vitro antibacterial activity of curcumin alone and associated with oxacillin against MRSA strains, to analyze the mechanism of cell death involved in the isolated action of curcumin by means of flow cytometry and molecular docking, and to verify its superbiofilm action. Curcumin showed antibacterial activity in the range of 125–500 μg/mL against the tested strains, since it caused an increase in membrane permeability and DNA fragmentation, as revealed by flow cytometry analysis. Moreover, it was possible to observe interactions of curcumin with wild-type S. aureus DHFR, S. aureus gyrase and S. aureus gyrase complex with DNA, DNA (5′-D(*CP*GP*AP*TP*GP*CP*G)-3′) and Acyl-PBP2a from MRSA by molecular docking. Curcumin also had a synergistic and additive effect when associated with oxacillin, and significantly reduced the cell viability of the analyzed biofilms. Thus, curcumin is a possible candidate for pharmaceutical formulation development for the treatment of MRSA infections.
... 2,76 The therapeutic effects of curcumin are limited by poor aqueous solubility, low bioavailability, and fat metabolism. 70,73,74,77 To improve the efficiency of curcumin, water-soluble curcumin derivatives have been developed. 76,78 Abdel Aziz et.al 76 investigated a novel water-soluble curcumin derivative. ...
Article
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Introduction: The use of current available treatment for male erectile dysfunction (ED) has some limitations that are related to efficacy and adverse effects. Nanotechnology has been used as a new tool in medicine to improve these limitations and new medications potentially to alleviate and cure ED. Aim: To review the currently literature on new nano medications for ED based on scientific and clinical studies, efficacy, safety, mechanisms of action, and to identify gaps for future research. Methods: A comprehensive literature review was conducted via Google Scholar, Science Direct, and PubMed on English publications using different keywords such as "erectile dysfunction", "emerging treatments", "nanotechnology", and "herbal medicine". The retrieved papers were organized into groups according to the sections covered in this review paper. Main outcomes measures: We reviewed novel ED treatments such as nanotechnological phosphodiesterase inhibitors, papaverine hydrochloride, sialorphin, adipose tissue-derived stem cells, sonic hedgehog, and herbal medicine. Results: Numerous preclinical studies have addressed novel phosphodiesterase 5 inhibitors nanoparticle, and their recent delivery systems. Nitric oxide, sialorphin, sonic hedgehog, and herbal medicine loaded nanoparticles and nano adipose tissue-derived stem cells as a potential new treatment for ED. In addition, papaverine-containing nanoparticles have been reported. A limited number of randomized clinical studies have determined the mechanism of these treatments. Conclusion: A literature review on the application of nanotechnology in ED therapy was successfully conducted. New nano medications are promising to treat ED. However, further studies are warranted to further assess their efficacy and safety. Masuku NP, Unuofin JO, Lebelo SL. Advances in Nanoparticle Delivery System for Erectile Dysfunction: An Updated Review. Sex Med 2021;XX:XXXXXX.
... Natural products, in general, are thought to have fewer side effects than synthetic medications. The usage of herbal remedies in dermatology are fast-growing, and several natural products proved to heal properties such as Aloe vera, curcumin, honey, tea tree oil, henna, asthma plant, and olive oil (Mohanty and Sahoo 2017;Tuhin et al. 2017;Minden-Birkenmaier and Bowlin 2018;Daemi et al. 2019;Aryani et al. 2020;Bardaa et al. 2021;Elmowafy et al. 2021;Melguizo-Rodríguez et al. 2021). Panahi et al. (2015) investigated the healing properties of Aloe vera/olive oil combination; however, the morphological, histological, and immunohistochemical analyses were missing. ...
Article
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Diabetic wounds are characterized by a delayed closure rate due to the excess inflammation and the inhibition of angiogenesis. Natural products derived from Aloe vera have shown great promise due to their healing magnificent properties. Olive oil is another natural product with anti-microbial and anti-inflammatory properties that may contribute to the healing process. In the present investigation, we tried to evaluate the efficacy of topical application of Aloe gel and/or olive oil in the enhancement of diabetic wounds using histological and immunohistochemical analysis. Excisional wounds were created on the back skin of streptozotocin-induced diabetic rats. Topical treatments of Aloe gel and/or olive oil were applied separately and in a combination (AVO) daily for experimental groups. Macroscopic and microscopic observations of the excision wounds were monitored at time intervals (3, 6, 9, 14 days) post-wounding. Macroscopic observations of the AVO group exhibited almost complete healing at day 14, while other groups were still in progress. Similarly, immunohistochemical analysis of the AVO group showed a mild expression pattern of NF-κB.. While, the cell proliferation (Ki-67), and angiogenesis (CD34) markers were upregulated. Conclusively, the obtained results showed that the AVO combination effectively improved the healing process in diabetic excisional wounds with significant differences in the healing kinetics compared to wounds that received Aloe gel or olive oil separately.
... Recent studies have shown that wounds treated with honey generally heal faster than untreated wounds [8,10]. Modernization has also inspired advancements in wound-healing strategies, for instance, the use of medicated topical creams [11][12][13] . ...
... Potential of administered drug to reach effectively in the target site on time is a big challenge in the pharmaceutical industry. Different topical formulations were developed and evaluated for their wound healing properties [16,17]. Advancement in nanotechnology have resulted in the development of both organic and inorganic nanoparticles based drug delivery systems, which possess greater potential to promote the wound healing [18,19]. ...
Article
Diabetes skin infection is a very common disorder in hyperglycemic patients. This study evaluated the prospective of developing a topical gel formulation of Aloe vera with insulin-loaded nanoemulsion and evaluates its potential for wound healing in diabetic rats. The insulin-loaded nanoemulsion was fabricated using oleic acid, tween 80, and polyethylene glycol 400 to achieve nano sized particles. Selected nanoemulsion (NE5) was incorporated in topical gel containing Aloe vera and control (without Aloe vera). The gels were characterized for in vitro, evaluated in vivo by biochemical, wound healing and histopathological analyses. The pharmaceutical properties of prepared gels indicate good spreadability, permeation and stability. The micrographs of gels showed uniform distribution of nano-sized spherical particles inside the macromolecular network of polymeric gels. Glucose and insulin levels in diabetic rats demonstrated significant antidiabetic effect (P < 0.0001) in the insulin treated groups as compared to the positive control. The wound healing effect substantiate the biochemical data as evidenced by greater wound contraction (75% in 15 days) with gel formulation containing insulin and Aloe vera. Histopathological examination revealed marked improvement in the skin histological architecture of treated groups. Skin irritation study signifies the formulated gel is nonirritant and is safe for topical use. This study concludes that Aloe vera with insulin-loaded nanoemulsion showed synergistic effect towards effective healing of the wound in diabetic rats, and could be a promising and effective approach in the treatment of wounds in diabetic patients.
... 3 In the United States, $20 billion dollars is spent annually on treating patients with chronic wounds and the international cost of wound treatment caused by sharp objects was estimated at $13 billion in 2008 and could reach $21 billion in 2021. 4,5 Chronic wounds have delayed wound healing due to exacerbation of the inflammatory phase. 6 In addition, wound healing processes can be impaired by certain pathological conditions, including diabetes mellitus, which is projected to affect around 439 million people worldwide by 2030. ...
Article
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The skin is the largest organ in the human body and its physical integrity must be maintained for body homeostasis and to prevent the entry of pathogenic microorganisms. Sodium alginate (SA) and polyvinyl alcohol (PVA) are two polymers widely used in films for wound dressing applications. Furthermore, blends between SA and PVA improve physical, mechanical and biological properties of the final wound healing material when compared to the individual polymers. Different drugs have been incorporated into SA/PVA‐based films to improve wound healing activity. It is noteworthy that SA/PVA films can be crosslinked with Ca2+ or other agents, which improves physicochemical and biological properties. Thus, SA/PVA associations are promising for the biomedical field, as a potential alternative for wound treatment. This review focuses on the main techniques for obtaining SA/PVA films, their physical–chemical characterization, drug incorporation, and the advantages and challenges of these films for wound healing. Different SA/PVA ratios provide formulations with versatile properties for various applications. Drugs loaded in SA/PVA‐based films improve wound healing outcomes. Crosslinking improved physicochemical and biological properties of SA/PVA‐based films.
... Free radical scavenging activity of curcumin plays an important role in the lipid peroxidation, DNA breakage and enzyme inactivation of microorganisms. Curcumin incorporated polymer scaffolds have already shown good release and antibacterial activity towards pathogenic strains (Kiti & Suwantong, 2020;Mohanty & Sahoo, 2017). In addition to curcumin bacterial cellulose based materials also have antibacterial properties (Zheng, Li, Luo, & Wang, 2020) (fonters in bioengineering). ...
Article
Traditional cotton gauze derived from cellulose has many limitations in the processes of wound healing. To overcome these hassles, we used cellulose nanofibers (CNF) incorporated with curcumin for the fabrication of wound healing 3D porous aerogel. Cellulose nanofibers synthesized from plant waste are promising sustainable nanomaterials due to their biocompatibility and biodegradability. Ionic cross linking with sodium alginate was performed to maintain the mechanical strength. SEM results revealed highly porous architecture that effectively promoted wound healing, as a result of macro- and micro-porous architecture and curcumin. In-vitro drug release studies showed a slow and steady release pattern. The 3D porous nano bio aerogel with curcumin significantly promoted the migration of fibroblast cells and had excellent antimicrobial activity against pathogenic microorganisms. In-vivo studies showed angiogenesis without rejection or inflammation of the scaffold. From the observations, we can conclude that this novel 3D porous aerogel can be used to treat chronic wounds.
... The antioxidant capacity of Cur is associated with the phenolic hydroxyl, the β-diketone moiety and the methoxy groups in its structure, which have the ability to shift electrons or provide H-atoms (Mohanty & Sahoo, 2017). The DPPH/ABTS assay is correlated to electron and hydrogen atom transfer, while the FRAP assay is related to electron transfer reaction (Prior, Wu, & Schaich, 2005). ...
Article
The food-derived peptides hydrolyzed from native food protein matrix exhibited various bioactivities and multimeric structures, which make them the promising well-defined nanoplatforms candidates to co-deliver themselves with other bioactive compounds. In this study, zein-egg white derived peptides-chitosan (Z-EWDP-CS) ternary nanoparticles (NPs) were successfully fabricated by the spontaneous assembly to enhance the stability and bioactivity of curcumin (Cur). The novel ternary NPs exhibited a typical nano-spherical structure (138.63 nm, 40.50 mV), and adorable encapsulation efficiency (EE, 93.87%) for Cur. FTIR, XRD and DSC results verified that Cur changed from a crystalline state to an amorphous state, and was successfully entrapped in the cavity of Z-EWDP-CS NPs. Furthermore, the thermal stability, photochemical stability, salt stability, and antioxidant activity were considerably improved in the NPs after the addition of EWDP. Our results demonstrate that the food-derived peptides could be an ideal affinity agent for the co-delivery of themselves with hydrophobic nutraceuticals.
... Because of their biocompatibility with and similarities to natural tissues, various natural medicines such as honey, 22 avocado, 23 curcumin, 24 aloe vera 25 and keratin, 26 have been used to provide protection against wound infection, with variable results. Incorporation of these materials into polymers can enhance their healing properties and reveal new functionalities of combined natural materials with polymers. ...
Article
Objective Hard-to-heal wounds, such as pressure ulcers and diabetic ulcers, are a major challenge for wound dressings. The aim of this study was to develop a bioactive dressing based on polymers and natural materials with unique biological and therapeutic properties. Method The dressing was composed of an active layer containing polyvinyl alcohol (PVA), honey, curcumin and keratin, and an upper layer with lower hydrophilicity comprising PVA to induce flexibility. Physicochemical properties of the dressing were characterised by Fourier transform infrared spectroscopy, field emission scanning electron microscopy, swelling behaviour and antibacterial measurements. A wound healing study was performed using an experimental rat model and two different compositions of the bioactive dressing were compared with a commercial wound dressing (Comfeel, Coloplast, Denmark). Histopathological evaluation was conducted for this purpose. Results Characterisation results showed that a smooth bilayer film with two homogenous but distinct layers was produced. The dressing also provided adequate moisture to the wound environment without infection and adhesion due to dryness occurring. Our results exhibited significant bactericidal activity against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria and improved the wound healing process without any scarring. Histopathological findings demonstrated a significant higher healing rate in vivo together with well-formed epidermis, granulation tissue formation and tissue contraction, when compared with the commercial wound dressing. Conclusion Our results demonstrated acceptable physical and healing effects for the novel bioactive wound dressing; however, more investigations are recommended.
... Curcumin/ Turmeric has antioxidant, analgesic, anti-inflammatory, antimicrobial, wound healing agent, has chemosensitizing and radiosensitizing properties (Nagpal and Sood, 2013). Previous studies have already shown that it is effective against proinflammatory cytokines, cyclooxygenase, prostaglandin E. (Maziero et al., 2018) Turmeric stands forefront in wound healing (Mohanty et al., 2017) Studies have proven turmeric/curcumin are effective in potentially malignant disorders like oral submucous fibrosis (Rai et al., 2019), oral lichen planus (Nosratzehi., 2018) A systematic review (Normando et al., 2019) due to few studies and heterogeneity was present among studies meta-analysis wasn't performed. A recent meta-analysis reported incidence of severity of oral mucositis(>grade2) alone and subgroup analysis weren't performed (Zhang et al., 2020). ...
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Background: Oral Mucositis(OM) is an acute debilitating dose limiting toxicity of Radiotherapy/Radiochemotherapy(RT/RCT) in management of Head and Neck Cancer (HNC). Curcumin/Turmeric may reduce OM in patients. Aim: Efficacy of Curcumin/Turmeric for preventing and ameliorating the onset and severity of RT/RCT induced OM was analysed in this review. Methods: A systematic literature search with meta-analysis were performed using Mesh terms in PubMed, Google scholar, Science Direct, Cochrane library and manual searching, articles published from 2010 to April 2021 were included. Clinical trials that studied the efficacy/effects of turmeric / curcumin in management of RT/RCT induced OM in HNC patients were included. Statistical Analysis were done to calculate the pooled Risk ratio at 95%confidence interval with significance at p.
Article
The skin provides a protective barrier against toxic environments and also offers a valuable route for topical drug delivery. The stratum corneum (SC) is the outermost layer of the skin and serves as the major barrier to chemical transfer through the skin. The human skin barrier is particularly diffcult to overcome because of the complex composition and structure of the SC. Nanoparticulate carriers have gained widespread attention in topical drug delivery due to their tunable and versatile properties. The present review summarizes the main factors involved in the skin penetration of nanocarriers containing drug. Employment of nanotechnology in topical delivery has grown progressively during recent years; however, it is important to monitor the skin penetration of nanocarriers prior to their use due to avoid possible toxic effects. Nanocarriers can act as a means to increase the skin permeation of drugs by supporting a direct interaction with the SC and increasing the period of permanence on the skin. The skin penetration is influenced by the physicochemical characteristics of nanocarriers such as composition, size, shape, surface chemistry as well as skin features. Considering that the target of topical systems based on nanocarriers is the penetration of therapeutic agents in the skin layers, so a detailed understanding of the factors influencing skin permeability of nanocarriers is essential for safe and efficient therapeutic applications.
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A presente pesquisa apresentou por objetivo a realização de uma pesquisa acerca da atividade antioxidante e anti-inflamatória apresentada pela espécie vegetal Curcuma longa Linn e foi desenvolvida através de levantamento bibliográfico com abordagem qualitativa de natureza descritiva, seguindo a metodologia descrita por Augusto et al. (2013). Os artigos foram selecionados nos bancos de dados DrugBank, Google acadêmico e Scielo. Os descritores de busca foram: Curcuma longa, funções biológicas, compostos bioativos, ação antioxidante, aplicação clínica da C. longa, ação anti-inflamatória e neutralização de radicais livres publicados no período de 2010 a 2020 nos idiomas inglês e português. A atividade anti-inflamatória da C. longa L. deriva de sua capacidade em inibir a produção de proteínas que fazem parte do processo inflamatório, atuando na supressão das cascatas sinalizadoras inflamatórias. Também sugere que o mecanismo pelo qual a cúrcuma expressa seu efeito é impedindo a produção da ciclooxigenase-2 (COX-2) além de inibir a expressão de interleucinas e fator de necrose tumoral-α (TNF- α) e ser capaz de intervir na via do ácido araquidônico e interrupção da atividade do fator nuclear κ B (NF)-κB. O óleo essencial dessa espécie apresenta atividade antioxidante devido à sinergia dos seus componentes dose-dependente sugerindo que o óleo expressa sua ação antioxidante devido a atração da doação de hidrogênio. Os extratos obtidos por extração ultrassônica manifestaram maior capacidade redutora e capacidade superior de eliminação dos radicais DPPH e ABTS. Além disso, os resultados também demonstraram que in vitro a C. longa L. apresenta potencial anticâncer considerável ao reduzir a produção de espécies reativas de oxigênio (EROs) intracelular, inibição da migração celular, indução de alterações morfológicas nas células e em material genético. Foi possível elucidar que a Curcuma longa L. apresenta capacidade anti-inflamatória e antioxidante comprovada in vitro, porém, ainda é perceptível a pouca demanda quando se trata de estudos in vivo principalmente em humanos. Também é possível comprovar a escassez de estudos brasileiros.
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Skin ulcers, wounds, or burns represent a burden for health care worldwide. Our aim was to explore the effects of mucoadhesive formulation with Curcuma longa L. extract mucoadhesive formulation containing curcumin (MFC) on skin healing in Wistar rats. Fifty-four rats were randomly allocated into 3 groups: control, vehicle, and MFC. A full-thickness circular wound was induced on the back of each animal. Two daily applications of the products were performed according to the experimental group. On days 3, 10, and 21, 6 animals in each group were euthanized. Clinical analysis was based on wound area. Histologic analysis was performed in hematoxylin and eosin-stained sections, with re-epithelization and inflammation being assessed by means of semiquantitative scores. To analyze the Akt/mTOR pathway, immunohistochemistry for phospho Akt (pAkt) and phospho ribosomal protein S6 were investigated. In addition, nuclear factor kappa-light-chain-enhancer of activated B cells immunolabeling was performed. Clinical analysis revealed wounds with a smaller area on days 3 and 10 in curcumin-treated animals. Histologically, MFC had a significant impact on inflammatory events on days 3 and 10 and promoted faster re-epithelization, which was evidenced on day 10. MFC-treated wounds exhibited pAkt upregulation on day 10 and both pAkt and phospho ribosomal protein S6 downregulation on day 21. Nuclear factor kappa-light-chain-enhancer of activated B cells expression varied through the evaluation periods; however, no significant difference was observed between groups. Collectively, our results indicate that MFC is efficient in accelerating cutaneous wound repair through modulation of the inflammatory process and stimulus of re-epithelization by an Akt/mTOR-dependent mechanism.
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Hydrogels are proving to be very versatile as wound healing devices. In addition to their capabilities of providing a moist cellular environment and adaptive mechanical properties mimicking the extracellular matrix, they allow the incorporation of small molecules, which have potential impacts on cellular behaviour, in their nanostructures. This strategy can allow for specific targeting of the different stages of wound healing namely hemostasis, inflammation, and proliferative and remodelling phases. The latter include interlinked processes such as angiogenesis, collagen synthesis, growth factor release, collagen maturation and re-epithelialization. In this review, we attempt to match the mechanisms of action of natural molecules/extracts to the different stages of wound healing so that they can be used in a novel approach of multiphase-directed tissue regeneration using loaded hydrogel scaffolds.
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Today, due to the prevalence of various diseases such as the novel coronavirus (SARS-CoV-2), diabetes, central nervous system diseases, cancer, cardiovascular disorders , and so on, extensive studies have been conducted on therapeutic properties of natural and synthetic agents. A literature review on herbal medicine and commercial products in the global market showed that curcumin (Cur) has many therapeutic benefits compared to other natural ingredients. Despite the unique properties of Cur, its use in clinical trials is very limited. The poor biopharmaceutical properties of Cur such as short half-life in plasma, low bioavailability, poor absorption, rapid metabolism , very low solubility (at acidic and physiological pH), and the chemical instability in body fluids are major concerns associated with the clinical applications of Cur. Recently, nanoformulations are emerging as approaches to develop and improve the therapeutic efficacy of various drugs. Many studies have shown that Cur nanoformulations have tremendous therapeutic potential against various diseases such as SARS-CoV-2, cancer, inflammatory, osteoporosis, and so on. These nanoformulations can inhibit many diseases through several cellular and molecular mechanisms. However, successful long-term clinical results are required to confirm their safety and clinical efficacy. The present review aims to update and explain the therapeutic potential of Cur nanoformulations. K E Y W O R D S bioavailability, biological applications, commercial nanoproducts, Curcumin, nanoformulations, therapeutic mechanisms
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Wound healing is a complicated process constituted of four successive physiological stages involving wound bleeding, inflammatory response, cell proliferation and tissue remodeling. During this period, bacteria can easily infect the wound. Therefore, we prepared a novel curcumin-loaded sandwich-like nanofibrous membrane (CSNM) using sequential electrospinning for the hemostasis, antibacterial and accelerate wound healing. The morphology of the nanofibrous membrane was analyzed by SEM. In addition, the water absorption capacity, water vapor transmission rate, water contact-angle, and in vitro drug release were all tested. Then in vitro and in vivo hemostatic experiments demonstrated that CSNM has a good hemostatic effect. Antioxidant effect was assessed by the DPPH radical scavenging method and CSNM presented a high antioxidant activity. Additionally, CSNM demonstrated excellent antibacterial activity by the disk diffusion method. Furthermore, the rat dorsal skin defects model revealed that the CSNM distinctly induced the granulation tissue grew, collagen deposition and epithelial tissue remodeling. Meanwhile, the results of the immunohistochemical staining showed that the CSNM can facilitate the expression of CD31 and TGF-β in the early stage of the wound, thereby accelerating wound healing. In general, this study proved that the multifunctional CSNM has great potential as wound dressing in wound healing.
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This review paper aimed to provide an insight on (1) the chemical structure and biological activity of curcumin, (2) physico-mechanical and antimicrobial properties of curcumin-loaded films, (3) the controlled release of curcumin from the film, and (4) the potential applications of the films incorporated by curcumin in food preservation. It was found that besides the inherent antimicrobial activity of curcumin, the medium in which curcumin has to execute its function is important. The intelligent packaging system based on curcumin/biopolymers can be used as an effective indicator to monitor animal-based protein foods' freshness. Overall, polysaccharide and/or protein composite films loaded with curcumin, as novel kinds of functional films could find applications in the food packaging industry.
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The moisture conditions and temperature changes are two key factors affecting wound management. Thermosensitive hydrogels are ideal dressing materials since they can maintain a moist environment at the wound site and release additional bioactive molecules to treat the wound when the area is infected. In this study, we developed a novel thermosensitive dressing based on cotton fabric as a matrix to provide robust mechanical properties. Inclusion complexes between cyclodextrins (HP-β-CD, DM-β-CD, and β-CDP) and curcumin were prepared and loaded into the thermosensitive dressing to obtain drug-release properties. The cotton coated with a thermosensitive polymer (CS-g-PVCL) that was crosslinked by citric acid to form a hydrogel was loaded with the appropriate inclusion complex chosen based on phase solubility studies. This composite dressing was investigated to characterize its wound management properties, such as the water vapor permeability and drug release behavior in response to the temperature. The resulting cytotoxicity, antibacterial, and antioxidant properties suggest the potential use of this thermosensitive-hydrogel-functionalized textile as an active wound dressing.
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Surgical resection of the tumor remains the preferred treatment for most solid tumors at an early stage, but surgical treatment often leads to massive bleeding and residual tumor cells. Therefore, a novel alginate/gelatin sponge combined with curcumin-loaded electrospun fibers (CFAGS) for rapid hemostasis and prevention of tumor recurrence was prepared by using an electrospinning and interpenetrating polymer network (IPN) strategy. The present results show that alginate/gelatin sponge display excellent hemostatic properties and possess more advantages than commercial gelatin hemostasis sponge. More importantly, CFAGS could control the release of curcumin, inducing curcumin to accumulate at the surgical site of the tumor, thereby inhibiting local tumor recurrence in the subcutaneous postoperative recurrence model. In addition, the sponge was safe to implant in the body and did not cause toxicity to normal tissues and organs. This approach represents a new strategy to implant a dual functional sponge at the postoperative site as an adjuvant to the surgical treatment of cancer.
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Electrospinning, a recent fast-emerging technique highly applicable in the production of nanofibers has gained vast recognition owing to its explicit applications in various domains. Amongst which, the production of nanoscaffolds for wound healing applications has been focused recently due to advantages over conventional wound healing methods. In the present research, a composite nanoscaffold comprising SBA-15 (Santa Barbara Amorphous), amine functionalized SBA-15 polycaprolactone (PCL) and curcumin was investigated for its potentiality in wound healing therapeutics. The high biocompatibility and cell adhesion of amine functionalized SBA-15 and the widely explored antimicrobial properties of curcumin added benefit for the wound healing target. The prepared highly interconnected electrospun fibers with porous structure were characterized through various studies such as FTIR, XRD, SEM and EDAX. Further, antibacterial studies against both Gram positive (Bacillus subtilis) and Gram negative (Escherichia coli) strains revealed an improved zone of inhibition. Major invitro studies such as cell migration, proliferation, bio-compatibility was experimented through cell adhesion and live and dead assay using Swiss 3T6 cell lines. In vivo studies on female Wister rats using the fabricated nanofibers incorporated with curcumin and amine functionalized SBA-15 showed 99% scar-less wound healing within 21 days. Re-epithelization of tissue, collagen deposition and formation of granulation tissue were observed from the results of Hematoxylin-Eosin and Masson's tri-chrome staining. From the observations, it can be concluded that the fabricated nanoscaffold could be an effective substrate for wound healing therapeutics.
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Insight is provided into the mechanism of peptide gelation, a self-assembled process of particular interest, due to its wide existence in natural events and broad applications in food and biomaterials field, but hard to control as minor alterations in the peptide sequence. Here, we design a family of pentapeptides and control their self-assembly behaviors, from micro- and nanoparticles to nanofibers and hydrogels. Furthermore, based on the thermodynamics, the gelation kinetics and the ionization status of terminal groups, the peptide assembly goes through five stages as varying the pH value and the assembly structures are highly dependent on the charging status of the terminal groups. The gelation rules of these peptides are further investigated. Besides, we also load hydrophobic functional molecule (curcumin) into different self-assembly nanostructures with high encapsulation efficiency and remarkable thermal and light protection on curcumin. These peptides assemblies with tunable structures, encapsulation ability and photothermal stabilization could become promising candidates for hydrophobic function factor delivery in food industry.
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Paracetamol has analgesic properties comparable to NSAIDs, but paracetamol have minimal side effects. Paracetamol is metabolized via sulfation and glucuronidation conjugation which is then excreted in the urine. A small part of the paracetamol has been changed to NAPQI. NAPQI will be detoxified by gluthathione. In high doses, there in an increase in NAPQI and a decrease in glutathione levels that results in oxidative stress and liver cell necrosis. Curcumin is often used as a traditional medicine to treat liver disease where it contains phenolic groups capable to scavenge free radicals. Curcumin extract can improve cellular responses to oxidative stress such as increasing the expression of Nrf2, SOD, and gluthathione. The purpose of this research was to know the effect of curcumin on the improvement of liver function in white rats (Rattus novergicus) induced by high dose paracetamol. The design of this research was a descriptive research using literature studies from at least 15 international journals indexed by Scimago or national journals indexed by Sinta published in 2015-2020. Based on the journals used in this research, giving curcumin at a dose of 200 mg/kg BW/day for 2 weeks was effective in significantly increasing gluthathione levels in rats receiving high dose paracetamol. Giving curcumin at a dose of 100 mg/kg BW/day for 7 days can reduce AST and ALT activity in rats receiving high dose paracetamol, but the dose of curcumin that was more effective in reducing AST and ALT activity was 200 mg/kg BW/day for 2 weeks. This is because of curcumin which functions as a hepatoprotector that bind directly to the toxic metabolite of paracetamol, thereby reducing the use of glutathione and quench free radicals, so that oxidative stress in the liver decreased and gluthathione levels increased, AST and ALT activity decreased.
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Chronic wounds cannot proceed through the normal, orderly, and timely sequence of repair. The adverse cycle between excess reactive oxide species (ROS) and a persistent inflammatory response is an important mechanism of impaired wound healing. Herein, by combining the intrinsic bioactivities of natural polysaccharides and natural drugs, a glycosaminoglycan-based hydrogel delivery system is proposed to regulate the wound microenvironment. Dynamic supramolecular cross-linking enables the hydrogel to easily encapsulate the drug and fully fill the wound area. As the backbone of the hydrogel, heparin captures inflammatory chemokines at the wound site, while hyaluronic acid mimics the function of ECM. The hydrophobic drug curcumin has been ingeniously encapsulated in the hydrogel through micellization, thereby exerting good ROS scavenging ability and anti-inflammatory activity. Evaluations in diabetic mice showed that this antioxidant and anti-inflammatory hydrogel was effective in reducing the influx of immune cells at the wound site and in down-regulating the inflammatory response. Accelerated wound healing was also observed, as evidenced by faster re-epithelialization and better ECM remodeling. The proposed hydrogel can regulate the microenvironment of wounds from multiple aspects and thereby achieve regression of wound repair, which may provide a new therapeutic strategy for chronic wounds.
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Curcumin, a principal component of Curcuma longa, has a long history of being used topically for wound healing. However, poor aqueous solubility of curcumin leads to poor topical absorption. Recently, gelatin based gel has been reported to overcome this issue. However, the release of curcumin from gelatin gel in the bioavailable or easily absorbable form is still a challenge. The present study reports the development of a composite gel prepared from gelatin, F127 and lecithin using temperature dependant gelation and loading of curcumin within it. Notably, the composite gel facilitated the release of curcumin entrapped within vesicles of ~400 nm size. Further, the composite gel exhibited increase in the storage modulus or gel strength, stability, pore size and hydrophobicity as compared to only gelatin gel. Finally, wound healing assay in murine model indicated that curcumin delivered through composite gel showed a significantly faster healing as compared to that delivered through organic solvent. This was also validated by histopathological and biochemical analysis showing better epithelization and collagen synthesis in the group dressed with curcumin containing composite gel. In conclusion, composite gel facilitated the release of bioavailable or easily absorbable curcumin which in turn enhanced the wound healing.
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Curcumin is a polyphenolic active ingredient found in the Curcuma Longa plant (Turmeric). It is a member of the Zingiberaceae family. Turmeric and its compounds are used to treat a variety of diseases in underdeveloped nations because to their low cost. It's a common ingredient in herbal medicine. As an antioxidant, antifungal, antibacterial, anti-inflammatory, and anti-cancer agent, it has a lot of promise. Diabetes mellitus, arthritis, diabetic microangiopathy, gastro-intestinal illness, psoriasis, diabetic nephropathy, anxiety, bacterial infection, hyperlipidemia, acute cardiac disease and inflammation are only of few the disorders and symptoms for which it is very helpful. Although curcuma longa is safe to use and has no negative effect or any toxic response on human health, it is best known for its positive effect in reducing infertility, lowering blood glucose level, reduce bleeding issue and heavy menstruation in some people. Curcumin is an anti-oxidant that played a vital role in the prevention of many illnesses.
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Effective hemostasis, antibacterial, and anti-inflammation are essential for wound healing, which, however, are hampered by the structural deficiencies of traditional wound dressings. Herein, we prepared a three-dimensional (3D) layered nanofiber sponge (3D-AgMOF-CUR), where silver-metal organic framework (Ag-MOF) was grown in situ and curcumin (CUR) was loaded, to promote the wound healing by timely absorbing exudate at the wound site, accelerating hemostasis, as well as resisting bacteria growth and inflammation. Nanostructure, water absorption capacity, porosity, elasticity and tensile properties, and drug release in vitro of the 3D-AgMOF-CUR were systemically characterized. Its outstanding hemostasis and coagulation effect were demonstrated by in vitro coagulation and blood suction tests. Experimental results from CCK-8 assay, disk diffusion and bacterial co-culture methods further evidenced the fantastic antibacterial effect and good cytocompatibility of the 3D-AgMOF-CUR. In addition, its high wound healing efficiency was confirmed in vivo, as revealed by improved wound healing efficiency and significantly decreased scar area during the healing process of a wound infection model. This study demonstrated that the layered 3D nanofiber sponge could shed light on the clinical wound healing in the future.
Article
This study developed and characterized the chitosan-functionalized Fe3O4@SiO2 nanoparticles (Fe3O4@SiO2@CS NP) as a drug delivery system. Fe3O4 NP were first synthesized by co-precipitation method, followed by coating with SiO2, and functionalized with chitosan via glutaraldehyde crosslinking bridges. The newly synthesized Fe3O4@SiO2@CS NP possessed an octagonal shape with a diameter of ~ 20 nm. In the FT-IR spectrum, the Fe3O4@SiO2@CS NP demonstrated the appearances of C–O, N–H, and C–H peaks, indicating the presence of chitosan in their structures. The Fe3O4@SiO2@CS NP could preserve the Fe3O4 magnetic property with a magnetization value of 52.43 emu/g, a magnetization remanence of almost 0 emu/g, and minimal residual coercivity. Utilizing curcumin as a drug model, the Fe3O4@SiO2@CS NP could adsorb the drug rapidly, to more than 71% within 20 min, with an adsorption capacity of 6.54 mg/g and an adsorption energy of 0.2029 kJ/mol (following the Dubinin–Radushkevich model). The curcumin adsorption process was in good agreement with the pseudo-second-order kinetics (R2 = 0.9975). Interestingly, in the simulated body fluid, the curcumin-loaded Fe3O4@SiO2@CS NP could retain the curcumin release, with no detectable drug release, in the first hour, followed by a burst release within the next hour. This confirms the contribution of CS in the system. Conclusively, the Fe3O4@SiO2@CS NP could be further developed to potentially become a controlled-release drug delivery system.
Chapter
The use of the healing properties of medicinal plants dates back to ancient times. Herbal products are included in the traditional medicine of many countries. Nowadays, with the advancement in technology and the illumination of structures, bioactive components responsible for the activity in plants can be easily isolated. Thus herbal products can be manufactured by directly using herbal bioactive ingredients. Medicines used in the treatment of ocular diseases are generally applied topically. However, ocular barriers have the capability to reduce the bioavailability of drugs. For this reason, in recent years, using innovative drug delivery systems, it is aimed to increase the duration of drugs in the eye, to obtain extended drug release and increase their bioavailability. In this section, the use of herbal bioactives and natural excipients in the ocular field and their application to the eye as drug delivery systems are examined.
Chapter
Polyphenols, flavonoids, and related herbal bioactives are well known for their antioxidant, antiinflammatory, and antiinfectious activities. The biotherapeutic properties of these small molecules are precisely well suited for wound healing applications and interventions wherein they (1) assist with reduction in inflammation, initiate the first steps in tissue regeneration, and hence accelerate the healing process, (2) show free-radical scavenging activity, thereby preventing oxidative damage of the tissues, and (3) augment the action of antiinfective agents. However, the major disadvantages of these molecules such as low aqueous solubility, formulation instability, therapeutic efficacy at high concentrations, localized toxicity because of dose dumping, and rapid clearance from the site of action (the wound bed being very vascular) require specialized matrix-based strategies for their effective delivery and performance.
Article
This project purposes to develop chitosan and sodium alginate-based hydrogel membranes loaded with curcumin through microwave-based physical cross-linking technique and its evaluation for wound healing potential. For the purpose, curcumin-loaded chitosan and sodium alginate membranes were developed using microwave at fixed frequency of 2450 MHz, power 350 W for 60 s, and tested for their physicochemical attributes like swelling, erosion, surface morphology, drug content, and in vitro drug release. The membranes were also subjected to tensile strength and vibrational and thermal analysis followed by testing in vivo on animals. The results indicated that microwave treatment significantly enhanced the swelling ability, reduced the erosion, and ensured smooth surface texture with optimal drug content. The drug was released in a slow fashion releasing total of 41 ± 4.2% within 24-h period with a higher tensile strength of 16.4 ± 5.3 Mpa. The vibrational analysis results revealed significant fluidization of hydrophilic domains and defluidization of hydrophobic domains which translated into a significant rise in the melting temperature and corresponding enthalpy which were found to be 285.2 ± 3.2 °C and 4.89 ± 1.4 J/g. The in vivo testing revealed higher percent re-epithelialization (75 ± 2.3%) within 14 days of the treatment application in comparison to only gauze and other treatments applied, with higher extent of collagen deposition having well-defined epidermis and stratum corneum formation. The microwave-treated chitosan-sodium alginate hydrogel membranes loaded with curcumin may prove to be another alternative to treat skin injuries. Graphical Abstract.
Article
The surface structure and topography of biomaterials play a crucial role in directing cell behaviors and fates. Meanwhile, asymmetric dressings that mimic the natural skin structure have been identified as an effective strategy for enhancing wound healing. Inspired by the skin structure and the superhydrophobic structure of the lotus leaf, an asymmetric composite dressing was obtained by constructing an asymmetric structure and wettability surface modification on both sides of the sponge based on electrospinning. Among them, the collagen and quaternized chitosan sponge was fabricated by freeze-drying, followed by an aligned poly(ε-caprolactone) (PCL)/gelatin nanofiber hydrophilic inner layer and hierarchical micronanostructure PCL/polystyrene microsphere highly hydrophobic outer layer constructed on each side of the sponge. The proposed asymmetric composite dressing combines topological morphology with the material's properties to effectively prevent bacterial colonization/infection and promote wound healing by directing cellular behavior. In vitro experimental results confirmed that the aligned nanofiber inner layer effectively promotes cell adhesion, proliferation, directed cell growth, and migration. Meanwhile, the sponge has good water absorption and antibacterial properties, while the biomimetic hydrophobic outer layer exhibits strong mechanical properties and resistance to bacterial adhesion. In vivo results showed that the composite dressing can reduce inflammatory response, prevent infection, accelerate angiogenesis and epithelial regeneration, and significantly accelerate the healing of severe burns. Thus, the proposed bionic asymmetric dressing is expected to be a promising candidate for severe burn wound healing.
Article
Diabetic foot ulcers (DFUs) are a devastating ailment for many diabetic patients with increasing prevalence and morbidity. The complex pathophysiology of DFU wound environments has made finding effective treatments difficult. Standard wound care treatments have limited efficacy in healing these types of chronic wounds. Topical biomaterial gels have been developed to implement novel treatment approaches to improve therapeutic effects and are advantageous due to their ease of application, tunability, and ability to improve therapeutic release characteristics. Here, we provide an updated, comprehensive review of novel topical biomaterial gels developed for treating chronic DFUs. This review will examine preclinical data for topical gel treatments in diabetic animal models and clinical applications, focusing on gels with protein/peptides, drug, cellular, herbal/antioxidant, and nano/microparticle approaches. Statement of Significance : By 2050, 1 in 3 Americans will develop diabetes, and up to 34% of diabetic patients will develop a diabetic foot ulcer (DFU) in their lifetime. Current treatments for DFUs include debridement, infection control, maintaining a moist wound environment, and pressure offloading. Despite these interventions, a large number of DFUs fail to heal and are associated with a cost that exceeds $31 billion annually. Biomaterials have been developed to help target specific impairments associated with DFU with the goal to improve healing. A summary of these approaches is needed to help better understand the current state of the research.. This review summarizes recent research and advances in topical biomaterials treatments for DFUs.
Article
Inflammation and excessive reactive oxygen species production are the main reason for slow wound healing, which necessitates an efficient therapy in clinic. In the present study, curcumin-enveloped methoxy poly(ethylene glycol)-poly(δ-valerolactone)-poly(ϵ-caprolactone) (MPEG-PVL-PCL) micelles were prepared and embedded into Carbopol 940 hydrogel for full thickness dermal wound therapy. It was found that the prepared hybrid hydrogel had acceptable skin deposition and permeation, high antioxidant activity, and continuous erosion with sustained curcumin release. In the mouse ear edema model, when induced by croton oil, the anti-inflammatory activity of the hydrogel was better than that of dexamethasone sodium phosphate cream. An in vivo full thickness wound model in Kunming mice was established to evaluate the wound healing effect of the hydrogel. Wound closure, hydroxyproline/DNA content, and histological studies confirmed that the curcumin micelles-embedded hydrogel could promote collagen enrichment and improve re-epithelialization of the epidermis at the wound site. In summary, the curcumin-loaded MPEG-PVL-PCL micelles-embedded Carbopol 940 hydrogel was demonstrated to be a potential candidate for the treatment of skin inflammation and full thickness wound healing. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.
Chapter
A lot of advancements have taken place in the wound dressing materials and in wound healing process. Alginate based wound dressings materials are more preferable due to their biocompatibility and non-toxic unique biological characteristics. There’s always a need to increase the efficacy of alginates by combining with other biopolymers like chitosan, collagen and cellulose etc. However, the recent trend towards the natural and herbal bio-compounds are more likely attracting to develop alginate based wound dressing materials with higher efficiency, antimicrobial and anti-inflammatory potency. Out of many natural compounds tested, curcumin has shown high potency and more effectively used for wound healing purpose. Due to curcumin’s bio-medical properties it has been used as a vital ingredient combined with alginate and other biopolymers to prepare wound dressing materials. Based on the available literatures, this review chapter on alginate-curcumin nanocomposite will help the reader to develop better wound healing materials with evolutionary therapeutic applications.
Article
Bacterial induced wound infection is very common in real life, but the abuse of antibiotics means that is poses a potential threat to human health. The development of non-antibiotic type antibacterial materials appears to be of importance. Herein, a microenvironment-responsive and biodegradable hydrogel complex, consisting of an acid-degradable antibacterial hydrogel and a hydrogen peroxide (H2O2)-responsive polymer/gold hybrid film with photothermal conversion ability was constructed based on polyethylenimine (PEI), polyethylene glycol (PEG), hexachlorocyclic triphosphonitrile (HCCP), and gold nanoparticles. The resultant hydrogel showed excellent adhesion to various surfaces, whether in air or underwater. However, a simple glycerine and water (v/v = 1/1) mixed solution could rapidly promote the detachment of the hydrogel from skin automatically, without any external force and no residue was left, exhibiting a manmade controllable flexible feature. Moreover, the in vitro antibacterial performance against methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus (S. aureus), as well as wound healing investigations conducted in living mice confirmed that these hydrogels possessed excellent antibacterial, antioxidative, and wound healing abilities. We believe this proof of concept could create a novel pathway for the design and construction of highly efficient hydrogel dressings using readily available polymeric materials and that the resulting dressing have potential for clinical applications.
Article
Sesamin, a significant lignin compound isolated from sesame (Sesamum indicum Linn), is well known for its antioxidant, anti-inflammatory, and tissue growth promotion properties. Bioabsorbable poly(ε-caprolactone) (PCL) is also a well-known polymer applied to various fields of medicine as biomaterials. The main objective of this research was to produce a prototype material from PCL and sesamin by electrospinning technique for bone tissue engineering applications. Dichloromethane and dimethylformamide (7:3) mixture was used as the solvent system for fabrication of PCL nanofiber with different loads of sesamin concentrations (1–6 wt%). The crystallinity levels decreasing and the entrapment efficiency increasing (86.87%–93.97%) were observed while sesamin concentrations were increased. The infrared spectra of electrospun mats confirmed that sesamin corporated into fibrous networks. The sesamin-loaded PCL nanofibrous membranes showed a significant release of sesamin in the range of 1.28–8.16 μg/mL within 10 weeks. The release data were fitted to zero order, first order, Higuchi and Korsmeyer-Peppas models to evaluate sesamin-releasing mechanisms and kinetics. The releasing kinetics of sesamin followed the Fickian diffusion mechanism of Korsmeyer-Peppas (R² = 0.99). In vitro experiments with an osteosarcoma cell line (MG-63) revealed cell attachment, biocompatibility, and promotion of bone marker expression, the alkaline phosphatase (ALP) activity were studied. The electrospun PCL nanofiber loaded with sesamin had the potential as a scaffold for sesamin delivery to bone cells and applications in biomedicine.
Article
The aim of this study is to introduce an inspiring biomimetic system based on the red blood cell membrane (RBCM) vesicles for improved encapsulation efficiency and release of curcumin (Cur). Here, the role of the sonication time (0.5, 1.5, 3 and 5 min) on the properties of RBCM-CUR vesicles is investigated. It is determined that the hydrodynamic vesicle size, zeta potential, and release behavior are tunable by changing the sonication time. Noticeably, the average size of vesicles decreased from 163.0 ± 21 nm to 116.3 ± 16 nm by increasing the sonication time from 0.5 to 5 min. Moreover, the drug release value, after 24h incubation, enhances from 57 to 99% with the expansion of sonication from 0.5 to 5 min. Additionally, the entrapment efficiency of Cur as a model drug is high in whole sonication time, owing to the amphiphilic nature of RBCM. Finally, the RBCM-CUR vesicles are not only cytocompatible, but also could support the attachment and proliferation of fibroblast cells in vitro. The RBCM based system for delivery of Cur could be a promising system for the wound healing applications.
Article
Skin injury caused by large doses of ionizing radiation is the common and severe side effect of radiotherapy. However, its therapeutic efficacy is always hindered by early reactive oxygen species generation, repetitive inflammatory microenvironment and bacterial infection risk. Herein, we report an anti-biofouling hydrogel with anti-inflammation and anti-oxidative properties for the treatment of the irradiation-induced skin injury. The anti-biofouling hydrogel can be achieved by balancing of oppositely charged alginate, hyaluronic acid (HA) and ploylysine (PLL) at the optimal ratio, which effectively resist protein and bacterial adhesion and evade immune response. Moreover, curcumin and epigallocatechin gallate (EGCG) can be facially encapsulated and substantial released from the hydrogel. Results showed that the resulting AHP-Cur/EGCG hydrogel can significantly weaken the development of skin injury and accelerate its healing process by alleviating inflammation, scavenging ROS and promoting angiogenesis. Therefore, findings presented in this work provide an effective strategy for clinical management and treatment of ionizing radiation-induced skin injury.
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The pharmacological effects of curcumin can be ascribed to its dose–dependent activity. Therapeutic application of curcumin is hindered by its poor solubility and low bioavailability. Carbon dots are gaining attention in biomedical applications in view of their unique photo-physical properties. Some carbon dots derived from bioactive molecules have shown superior activity than the parent compound. With an aim to address the limitations of curcumin, herein we compared the wound healing activity of curcumin-derived carbon dots (CurCD) with curcumin. The improved solubility and stability of CurCD, combined with its superior proliferative, proangiogenic and anti-bacterial activity suggested that CurCD would be more beneficial than curcumin in wound healing. To enable the sustained release of CurCD at the wound site, a protease-responsive hydrogel (GHCD) was prepared with CurCD acting as a cross-linker. A comparative study using a skin excision model revealed that GHCD supported faster wound closure with improved angiogenesis and complete restoration of the epithelium. Apart from the establishment of CurCD as a wound healing agent, the study provides a novel carbon dot based approach for molecules with limitations of solubility and bioavailability.
Chapter
Nanotechnology is a new discipline of science that works with particles with sizes ranging from 1 to 100 nanometers. Nanotechnology is growing rapidly in the medical area, with applications, such as gene therapy, photodynamic therapy, radiation, radiofrequency therapy, and cancer therapy, among many others. It is also useful in engineering for the construction of nanoscale devices, including quantum dots, nanoshells, gold nanoparticles, and carbon nanotubes. The development of nanoparticles for diagnostic and screening purposes, as well as the development of artificial cellular proteins, such as receptors, DNA, and protein sequencing using nanospores and nanosprays, the manufacture of novel drug delivery systems, and tissue engineering are all examples of nanotechnology applications. Nanocrystals in immunohistochemistry, glucose monitoring in vivo using nanosensors, detection of disease biomarkers, detection of single nucleotide polymorphisms, and detection of microbes are all examples of nanodiagnostics applications. Nanotechnology‐based drug delivery is less harmful, and it may be used to deliver drugs to specific tissues. It can also be used to construct nanoporous membranes for controlled drug delivery. However, the disadvantage of this technology is that it is quite expensive, and the cost of development is extremely high. Nanotherapies could, thus, be far more cost‐efficient, effective, and safe in the long run and could drastically cut the cost of existing medical operations. The fundamentals of nanotechnology, applications, various developments, advantages, and downsides are explored in this chapter. Finally, the opportunities for clinical challenges posed by nanotechnology were examined in this outlook.
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Xiaoling Li,1 Xianlong Ye,2 Jianying Qi,2 Rangrang Fan,1 Xiang Gao,1 Yunzhou Wu,2 Liangxue Zhou,1 Aiping Tong,1 Gang Guo1 1State Key Laboratory of Biotherapy and Cancer Center, Department of Neurosurgery, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, People’s Republic of China; 2College of Life Science, Northeast Agriculture University, Harbin, People’s Republic of China Abstract: Wound healing is a complex multifactorial process that relies on coordinated signaling molecules to succeed. Epidermal growth factor (EGF) is a mitogenic polypeptide that stimulates wound repair; however, precise control over its application is necessary to reduce the side effects and achieve desired therapeutic benefits. Moreover, the extensive oxidative stress during the wound healing process generally inhibits repair of the injured tissues. Topical applications of antioxidants like curcumin (Cur) could protect tissues from oxidative damage and significantly improve tissue remodeling. To achieve much accelerated wound healing effects, we designed a novel dual drug co-loaded in situ gel-forming nanoparticle/hydrogel system (EGF-Cur-NP/H) which acted not only as a supportive matrix for the regenerative tissue, but also as a sustained drug depot for EGF and Cur. In the established excisional full-thickness wound model, EGF-Cur-NP/H treatment significantly enhanced wound closure through increasing granulation tissue formation, collagen deposition, and angiogenesis, relative to normal saline, nanoparticle/hydrogel (NP/H), Cur-NP/H, and EGF-NP/H treated groups. In conclusion, this study provides a biocompatible in situ gel-forming system for efficient topical application of EGF and Cur in the landscape of tissue repair. Keywords: epidermal growth factor, EGF, curcumin, wound healing, thermosensitive hydrogel, nanoparticles
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The aim of this study was to investigate the feasibility of Curcumin patches formulation (CPF) as a transdermal therapeutic system for wound healing potential. A combination of Poly Vinyl Pyrrolidone (PVP) and Ethyl Cellulose (EC) most strongly enhanced the permeation of Curcumin patch which permeated through the skin could effectively pass into the systemic circulation and attend therapeutic concentration. All formulation showed good physicochemical properties like thickness, weight variation, drug content, folding endurance, moisture content.The drug release through the transdermal patches of Curcumin follows first order kinetics with diffusion controlled mechanism. The results showed wound healing and repair is accelerated by applying CPF-1 formulation of the wound area by an organized epidermis. Study on animal models showed enhanced rate of wound contraction and drastic reduction in healing time than control, which might be due to enhanced epithelialization. The animals treated with Vicco-turmeric Cream and CPF-1 Formulation showed significant (* p< 0.01) wound healing results when compared with control groups. The treated wound after nine days itself exhibit marked dryness of wound margins with tissue regeneration. Group treated with CPF-1 formulation showed better wound closure compared to control group. Histopathological studies of Curcumin patches showed well-organized collagen fibers, increased in fibroblast cells and new blood vessels formation as compared to control group.
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It is extensively verified that continued oxidative stress and oxidative damage may lead to chronic inflammation, which in turn can mediate most chronic diseases including cancer, diabetes, cardiovascular, neurological, inflammatory bowel disease and pulmonary diseases. Curcumin, a yellow coloring agent extracted from turmeric, shows strong anti-oxidative and anti-inflammatory activities when used as a remedy for the prevention and treatment of chronic diseases. How oxidative stress activates inflammatory pathways leading to the progression of chronic diseases is the focus of this review. Thus, research to date suggests that chronic inflammation, oxidative stress, and most chronic diseases are closely linked, and the antioxidant properties of curcumin can play a key role in the prevention and treatment of chronic inflammation diseases.
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The increased risk of disease and decreased capacity to respond to tissue insult in the setting of aging results from complex changes in homeostatic mechanisms, including the regulation of oxidative stress and cellular heterogeneity. In aged skin, the healing capacity is markedly diminished resulting in a high risk for chronic wounds. Stem cell-based therapies have the potential to enhance cutaneous regeneration, largely through trophic and paracrine activity. Candidate cell populations for therapeutic application include adult mesenchymal stem cells, embryonic stem cells and induced pluripotent stem cells. Autologous cell-based approaches are ideal to minimize immune rejection but may be limited by the declining cellular function associated with aging. One strategy to overcome age-related impairments in various stem cell populations is to identify and enrich with functionally superior stem cell subsets via single cell transcriptomics. Another approach is to optimize cell delivery to the harsh environment of aged wounds via scaffold-based cell applications to enhance engraftment and paracrine activity of therapeutic stem cells. In this review, we shed light on challenges and recent advances surrounding stem cell therapies for wound healing and discuss limitations for their clinical adoption. © 2015 S. Karger AG, Basel.
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Wound healing is a complex process involving many interdependent and overlapping sequences of physiological actions. The application of exogenous lactate released from poly (lactic-co-glycolic acid) (PLGA) polymer accelerated angiogenesis and wound healing processes. Curcumin is a well-known topical wound healing agent for both normal and diabetic-impaired wounds. Hence, we hypothesized that the PLGA nanoparticles encapsulating curcumin could much potentially accelerate the wound healing. In a full thickness excisional wound healing mouse model, PLGA-curcumin nanoparticles showed a twofold higher wound healing activity compared to that of PLGA or curcumin. Histology and RT-PCR studies confirmed that PLGA- curcumin nanoparticles exhibited higher re-epithelialization, granulation tissue formation and anti-inflammatory potential. PLGA nanoparticles offered various benefits for the encapsulated curcumin like protection from light degradation, enhanced water solubility and showed a sustained release of curcumin over a period of 8 days. In conclusion, we demonstrated the additive effect of lactic acid from PLGA and encapsulated curcumin for the active healing of wounds.
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Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn's disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin's pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF-κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E(2), prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the effect of curcumin has been investigated.
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Many facets of wound healing under redox control require a delicate balance between oxidative stress and antioxidants. While the normal physiology of wound healing depends on low levels of reactive oxygen species and oxidative stress, an overexposure to oxidative stress leads to impaired wound healing. Antioxidants are postulated to help control wound oxidative stress and thereby accelerate wound healing. Many antioxidants are available over the counter or by prescription, but only one, Medihoney®, has been specifically FDA approved for wound healing. Here we review the existing evidence for the use of antioxidants for wound healing, with a review of the pertinent animal and clinical studies. Natural products and naturally derived antioxidants are becoming more popular, and we specifically review the evidence for the use of naturally derived antioxidants in wound healing. Antioxidant therapy for wound healing is promising, but only few animal studies and even fewer clinical studies are available. Because only few products have undergone FDA approval, the consumer is advised to scrutinize them for purity and contaminants prior to use, and this may require direct contact with the companies that sell them. As a field of science, the use of antioxidants for wound healing is in its infancy, and future studies will better elucidate the role of antioxidants in wound healing.
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Wound healing consists of an orderly progression of events that re-establish the integrity of the damaged tissue. Several natural products have been shown to accelerate the healing process. The present investigation was undertaken to determine the role of curcumin on changes in collagen characteristics and antioxidant property during cutaneous wound healing in rats. Full-thickness excision wounds were made on the back of rat and curcumin was administered topically. The wound tissues removed on 4th, 8th and 12th day (post-wound) were used to analyse biochemical and pathological changes. Curcumin increased cellular proliferation and collagen synthesis at the wound site, as evidenced by increase in DNA, total protein and type III collagen content of wound tissues. Curcumin treated wounds were found to heal much faster as indicated by improved rates of epithelialisation, wound contraction and increased tensile strength which were also confirmed by histopathological examinations. Curcumin treatment was shown to decrease the levels of lipid peroxides (LPs), while the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), activities were significantly increased exhibiting the antioxidant properties of curcumin in accelerating wound healing. Better maturation and cross linking of collagen were observed in the curcumin treated rats, by increased stability of acid-soluble collagen, aldehyde content, shrinkage temperature and tensile strength. The results clearly substantiate the beneficial effects of the topical application of curcumin in the acceleration of wound healing and its antioxidant effect.
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Gene therapy was traditionally considered a treatment modality for patients with congenital defects of key metabolic functions or late-stage malignancies. The realization that gene therapy applications were much vaster has opened up endless opportunities for therapeutic genetic manipulations, especially in the skin and external wounds. Cutaneous wound healing is a complicated, multistep process with numerous mediators that act in a network of activation and inhibition processes. Gene delivery in this environment poses a particular challenge. Numerous models of gene delivery have been developed, including naked DNA application, viral transfection, high-pressure injection, liposomal delivery, and more. Of the various methods for gene transfer, cationic cholesterol-containing liposomal constructs are emerging as a method with great potential for non-viral gene transfer in the wound. This article aims to review the research on gene therapy in wound healing and possible future directions in this exciting field.
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Medical treatment of complicated acute and chronic wounds represents a persistent and increasing medical and economic problem in our health-care system. In this review, we discuss the potentials and limitations of current and future gene therapy for the treatment of complicated, acute and chronic wounds. Chronic non-healing wounds result in significant morbidity, prolonged hospitalization, lost time from work and enormous health-care expenses. There are constant efforts to improve the therapeutic modalities to local treatment of wounds. One of them is gene-therapy where the delivery of peptides directly into the wound provides a relatively new and exciting possibility. The two groups of peptides of particular interest are growth-factors and anti-microbial peptides. Gene delivery of these peptides provides not only the possibility of more targeted local delivery but also larger concentrations. Many new techniques for gene delivery to wounds have been developed in recent years. The combination of mechanical and viral or chemical vectors appear to have the greatest yield. This review provides an update on gene delivery to cutaneous wounds.
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Effective wound healing leads to restoration of tissue integrity and occurs through a highly organized multistage process involving various cell types. Currently, methods for wound healing assessment lack a structured system for analysis of quantitative parameters. We have established a unique quantitative assessment strategy of wound healing stages based on histological criteria. Distinctive immunohistochemical parameters including re-epithelialization, epidermal differentiation, cell migration, proliferation, inflammatory response as well as dermal closure, matrix distribution, and skin remodelling were identified and followed during the timeline of wound healing progression. Assessment was based on various defined characteristics and each stage-specific parameter was independently quantified for complete wound closure. This analysis allowed a follow-up of wound healing dynamics and identified the contribution of critical and specific parameters to wound healing physiology and pathology. In this review we demonstrate our assessment strategy of crucial wound healing events and introduce a unique quantification system for each of the processes involved in wound repair. We believe that our unique method can be utilized as a diagnostic platform for standardizing assessment of wound healing progression as well as a screening tool for potential therapies.
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Burn infection is a serious problem that delays wound healing and leads to death. Curcumin (Cur) has been shown to exhibit antioxidant, anti-inflammatory, antimicrobial and anticarcinogenic activity. However, its instability, extremely low aqueous solubility and bioavailability in physiological fluids may make it difficult to maintain local Cur concentrations above the minimum inhibitory concentration for burn infection treatment. The objective of this study was to construct complexes of Cur/gelatin microspheres (GMs) and porous collagen (Coll)-cellulose nanocrystals (CNCs) composite scaffolds for full-thickness burn infection treatment. The Cur/GMs/Coll-CNCs scaffolds had high porosity, available pore size, and a long and sustained Cur release profile. Furthermore, the composite scaffold exhibited remarkably strong antibacterial activity. Hence, we evaluated the wound-healing effects and antibacterial properties of Cur/GMs/Coll-CNCs scaffolds in a rat full-thickness burn infection model. The Cur/GMs/Coll-CNCs scaffold was able to prevent not only local inflammation but also accelerated dermis regeneration. Thus, we conclude that Cur/GMs/Coll-CNCs scaffolds can act as an effective dermal regeneration template for full-thickness burn wound infection healing in rats models. Copyright
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In the present study, various nanoemulsions were prepared using Labrafac PG + Triacetin as oil, Tween 80 as a surfactant and polyethylene glycol (PEG 400) as a co-surfactant. The developed nanoemulsions (NE1-NE5) were evaluated for physicochemical characterizations and ex-vivo for skin permeation and deposition studies. The highest skin deposition was observed for NE2 with 46.07% deposition amongst all developed nanoemulsions (NE1-NE5). Optimized nanoemulsion (NE2) had vesicle size of 84.032 ± 0.023 nm, viscosity 78.23 ± 22.2 cps, refractive index 1.404. Nanoemulsion gel were developed by incorporation of optimized nanoemulsion (NE2) into 1–3% chitosan and characterized by physical evaluation and rheological studies. Chitosan gel (2%) was found to be suitable for gelation of nanoemulsion based on its consistency, feel and ease of spreadability. The flux of nanoemulsion gel was found 68.88 μg/cm²/h as compared to NE2 (76.05 μg/cm²/h) is significantly lower suggesting limited skin permeation of curcumin form gel. However, the retained amount of curcumin on skin by gel formulation (980.75 ± 88 μg) is significantly higher than NE2 (771.25 ± 67 μg). Enhanced skin permeation of NE2 (46.07%) was observed when compared to nanoemulsion gel (31.25%) and plain gel (11.47%). The outcome of this study evidently points out the potential of curcumin entrapped nanoemulsion gel in wound healing.
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Curcumin is one of promising agents to accelerate the wound-healing process. However, the efficacy of curcumin is limited due to its poor water solubility and stability. To enhance the properties of curcumin, 2-hydroxypropyl-γ-cyclodextrin (HP-γ-CyD) can be used through complexation. Recently, we revealed that sacran has the potential to form a hydrogel film (HGF) as a wound dressing material. Therefore, in the present study, we investigated the wound healing ability of curcumin/HP-γ-CyD (Cur/HP-γ-CyD) complex in sacran-based HGF (Sac-HGF). We prepared the Cur/HP-γ-CyD complex in Sac-HGF without surface roughness. Additionally, the amorphous form in the Cur/HP-γ-CyD complex in Sac-HGF were observed. In contrast, the curcumin in Sac-HGF and curcumin/HP-γ-CyD physical mixture in Sac-HGF formed inhomogeneous films due to crystallization of curcumin. Furthermore, HP-γ-CyD played an important role to increase the elastic modulus of the Sac-HGF with high re-swelling ability. The Cur/HP-γ-CyD complex in Sac-HGF maintained antioxidant properties of curcumin. Curcumin was gradually released from the HP-γ-CyD complex in Sac-HGF. Notably, the Cur/HP-γ-CyD complex in Sac-HGF provided the highest wound healing ability in hairless mice. These results suggest that the Cur/HP-γ-CyD complex in Sac-HGF has the potential for use as a new transdermal therapeutic system to promote the wound-healing process.
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The objective of this research was to develop novel curcumin- loaded nanostructured lipid carriers (Cur-NLCs) and Cur-NLCs based thermo-sensitive in situ gel (Cur-NLCs-Gel) for topical delivery. Cur-NLCs were prepared using the method of emulsion evaporation- solidification at low temperature and optimized with orthogonal design. The permeation ability of Cur-LNCs and Cur-NLCs-Gel were characterized in vitro. The results showed that the optimized Cur-LNCs represented uniform nano-sized spherical shape with the mean diameter of 263.9 nm. The entrapment efficiency and drug loading were 91.76% and 2.19%, respectively. And there was no significant difference between Cur-NLCs-Gel and Cur-NLCs in morphology, entrapment efficiency and drug loading at the room temperature. The cumulative penetration amount of Cur-NLCs and Cur-NLCs-Gel in vitro were 3.02 times and 2.42 times than that of curcumin propylene glycol solution, respectively. Moreover, in vivo study demonstrated Cur-NLCs-Gel showed the significant anti-inflammatory effect in auricle edemas mice and no obvious irritation to the abdominal skin of rat. Histopathology study of skin showed that Cur-NLCs-Gel could weaken the barrier function of stratum corneum and enhance the permeation of drug into skin. All the evidence showed that NLCs-Gel could provide a promising tuning as a dermal delivery system of curcumin.
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Diabetic wounds are a common complication in patients with diabetes that often lead to amputation. Although the pathophysiology of diabetic wound is multifactorial, chronic inflammation and lack of tissue regeneration leads to impair wound healing in diabetes. Application of curcumin (CUR) which is a well-known anti-inflammatory and antioxidant agent could be better strategy in diabetic wound healing. However, low bioavailability and poor stability of CUR hinders its application. Hence, in present study a novel nanohybrid scaffold has been prepared by incorporating CUR in chitosan nanoparticles (CSNPs) to improve stability and solubility followed by impregnation of prepared CUR-CSNPs into collagen scaffold (nanohybrid scaffold) for better tissue regeneration application. The prepared CUR-CSNPs were evaluated for particle size, zeta potential, SEM, differential scanning calorimetry and X-ray powder diffraction studies and the novel nanohybrid is evaluated for morphology, biodegradability, biocompatibility, in vitro drug release and in vivo wound healing studies. The results of NPs evaluation suggest the better stability and solubility of CUR. The nanohybrid scaffold showed good in vitro characteristics in terms of better water uptake, biocompatibility and sustained drug availability. The results of in vivo wound closure analysis revealed that nanohybrid scaffold treated wounds contracted significantly (p < 0.001) faster than the wounds from the control and placebo scaffold groups. Further, the obtained results suggest that complete epithelialization with thick granulation tissue formation occur in nanohybrid scaffold group, whereas lack of compact collagen deposition in placebo scaffold group and presence of inflammatory cells in control group was observed. Hence, the present study suggests that the synergistic combination of CUR (anti-inflammatory and anti-oxidant), chitosan (sustain drug carrier, wound healing) and collagen (established wound healer as scaffold) is a promising strategy to address various pathological manifestations of diabetic wounds and have better wound healing capability.
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Wound is a disruption of anatomic and physiologic continuity of the skin. According to the healing process, wounds are classified as acute and chronic wounds. A wound is considered chronic if standard medical procedures do not lead to the expected healing, or if the wound does not heal within six weeks. Chronic wounds are classified as typical and atypical. Typical wounds include ischemic, neurotrophic and hypostatic wounds. Diabetic foot and decubitus ulcers stand out as a specific entity among typical wounds. About 80 percent of chronic wounds localized on lower leg are the result of chronic venous insufficiency, in 5-10 percent the cause is of arterial etiology, whereas the remainder are mostly neuropathic ulcers. About 95 percent of chronic wounds manifest as one of the above-mentioned entities. Other forms of chronic wounds are atypical chronic wounds, which can be caused by autoimmune disorders, infectious diseases, vascular diseases and vasculopathies, metabolic and genetic diseases, neoplasm, external factors, psychiatric disorders, drug related reactions, etc. Numerous systemic diseases can present with atypical wounds. The primary cause of the wound can be either systemic disease itself (Crohn's disease) or aberrant immune response due to systemic disease (pyoderma gangrenosum, paraneoplastic syndrome). Although atypical wounds are a rare cause of chronic wounds, it should always be taken in consideration during diagnostic procedure.
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Reactive oxygen species (ROS) is a collective term used for oxygen containing free radicals, depending on their reactivity and oxidizing ability. ROS participate in a variety of chemical reactions with biomolecules leading to a pathological condition known as oxidative stress. Antioxidants are employed to protect biomolecules from the damaging effects of such ROS. In the beginning, antioxidant research was mainly aimed at understanding free radical reactions of ROS with antioxidants employing biochemical assays and kinetic methods. Later on, studies began to be directed to monitor the ability of anti-oxidants to modulate cellular signaling proteins like receptors, secondary messengers, transcription factors, etc. Of late several studies have indicated that antioxidants can also have deleterious effects on human health depending on dosage and bio-availability. It is therefore, necessary to validate the utility of antioxidants in improvement of human health in order to take full advantage of their therapeutic potential.
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In the present work new highly biocompatible nanovesicles were developed using polyanion sodium hyaluronate to form polymer immobilized vesicles, so called hyalurosomes. Curcumin, at high concentration was loaded into hyalurosomes and physico-chemical properties and in vitro/in vivo performances of the formulations were compared to those of liposomes having the same lipid and drug content. Vesicles were prepared by direct addition of dispersion containing the polysaccharide sodium hyaluronate and the polyphenol curcumin to a commercial mixture of soy phospholipids, thus avoiding the use of organic solvents. An extensive study was carried out on the physico-chemical features and properties of curcumin-loaded hyalurosomes and liposomes. Cryogenic transmission electron microscopy and small-angle X-ray scattering showed that vesicles were spherical, uni- or oligolamellar and small in size (112-220 nm). The in vitro percutaneous curcumin delivery studies on intact skin showed an improved ability of hyalurosomes to favour a fast drug deposition in the whole skin. Hyalurosomes as well as liposomes were biocompatible, protected in vitro human keratinocytes from oxidative stress damages and promoted tissue remodelling through cellular proliferation and migration. Moreover, in vivo tests underlined a good effectiveness of curcumin-loaded hyalurosomes to counteract 12-O-tetradecanoilphorbol (TPA)-produced inflammation and injuries, diminishing oedema formation, myeloperoxydase activity and providing an extensive skin reepithelization. Thanks to the one-step and environmentally-friendly preparation method, component biocompatibility and safety, good in vitro and in vivo performances, the hyalurosomes appear as promising nanocarriers for cosmetic and pharmaceutical applications. Copyright © 2015 Elsevier Ltd. All rights reserved.
Article
Despite its effectiveness, curcumin (Curc) dermal delivery is handicapped by hydrophobicity, high metabolism and poor skin permeation. In this work, the potential of novel self-assembled nanogels, namely gel-core hyaluosome (GC-HS) to enhance Curc delivery to wound sites, enhance healing rate and decrease scar formation was evaluated. Curc-GC-HS were prepared using film hydration technique and evaluated regarding size, zeta potential (ZP), entrapment efficiency (% EE), and in vitro release. Structure elucidation was performed using light, polarizing and transmission electron microscopy (TEM). In-vivo burn-wound healing potential, skin deposition ability and histological study were evaluated using female Sprague Dawley rats. Curc-GC-HS were compared to conventional transfersomal gel (Curc-T-Pl gel), and other conventional gels. Curc-GC-HS showed nanosize (202.7±0.66nm), negative ZP (-33±2.6mV) and % EE (96.44±1.29%). TEM revealed discrete vesicles with characteristic bilayer structure. Polarizing microscopy proposed liquid crystalline consistency. Burn-wound healing study showed that Curc-GC-HS was the only system exhibiting marked improvement at day 7 of treatment. At 11th day, Curc-GC-HS treated wounds showed almost normal skin with no scar confirmed by histological analysis. Curc-GC-HS showed five folds higher skin deposition compared to conventional Curc-T-Pl gel. To conclude, novel gel-core hyaluosomes elaborated are promising nanogels able to increase Curc skin penetration and dermal localization while protecting it against degradation. Future perspective encompasses assessing potential of novel nanocarrier for skin cancer therapy. Copyright © 2015. Published by Elsevier B.V.
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Turmeric (Curcuma longa) is a popular Indian spice that has been used for centuries in herbal medicines for the treatment of a variety of ailments such as rheumatism, diabetic ulcers, anorexia, cough and sinusitis. Curcumin (diferuloylmethane) is the main curcuminoid present in turmeric and responsible for its yellow colour. Curcumin has been shown to possess significant anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-mutagenic, anti-coagulant and anti-infective effects. Curcumin has also been shown to have significant wound healing properties. It acts on various stages of the natural wound healing process to hasten healing. This review summarises and discusses on recently published papers on the effects of curcumin on skin wound healing. The highlighted studies in the review provide evidence of the ability of curcumin to reduce the body's natural response to cutaneous wounds such as inflammation and oxidation. The recent literatures on the wound healing properties of curcumin also provide evidence for its ability to enhance granulation tissue formation, collagen deposition, tissue remodelling and wound contraction. It has become evident that optimising the topical application of curcumin through altering its formulation is essential to ensure the maximum therapeutical effects of curcumin on skin wounds.
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Lipid nanoparticles are currently receiving increasing interest because they permit the topical administration of proteins, such as recombinant human epidermal growth factor (rhEGF), in a sustained and effective manner. Because chronic wounds have become a major healthcare burden, the topical administration of rhEGF-loaded lipid nanoparticles, namely solid lipid nanoparticles (SLN) and nanostructured lipid carries (NLC), appears to be an interesting and suitable strategy for the treatment of chronic wounds. Both rhEGF-loaded lipid nanoparticles were prepared through the emulsification-ultrasonication method; however, the NLC-rhEGF preparation did not require the use of any organic solvents. The characterisation of the nanoparticles (NP) revealed that the encapsulation efficiency (EE) of NLC-rhEGF was significantly greater than obtained with SLN-rhEGF. The in vitro experiments demonstrated that gamma sterilisation is a suitable process for the final sterilisation because no loss in activity was observed after the sterilisation process. In addition, the proliferation assays revealed that the bioactivity of the nanoformulations was even higher than that of free rhEGF. Finally, the effectiveness of the rhEGF-loaded lipid nanoparticles was assayed in a full-thickness wound model in db/db mice. The data demonstrated that four topical administrations of SLN-rhEGF and NLC-rhEGF significantly improved healing in terms of wound closure, restoration of the inflammatory process, and re-epithelisation grade. In addition, the data did not reveal any differences in the in vivo effectiveness between the different rhEGF-loaded lipid nanoparticles. Overall, these findings demonstrate the promising potential of rhEGF-loaded lipid nanoparticles, particularly NLC-rhEGF, for the promotion of faster and more effective healing and suggest their future application for the treatment of chronic wounds.
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In the present work biocompatible quercetin and curcumin nanovesicles were developed as a novel approach to prevent and restore skin tissue defects on chronic cutaneous pathologies. Stable and suitable quercetin- and curcumin-loaded phospholipid vesicles, namely liposomes and PEVs (Penetration Enhancer-containing Vesicles), were prepared. Vesicles were made from a highly biocompatible mixture of phospholipids and alternatively a natural polyphenol, quercetin or curcumin. Liposomes were obtained by adding water, while PEVs by adding polyethylene glycol 400 and Oramix(®)CG110 to the water phase. Transmission Electron Microscopy, cryogenic-Transmission Electron Microscopy, and Small- and Wide-Angle X-ray Scattering showed that vesicles were spherical, oligo- or multilamellar and small in size (112-220 nm). In vitro and in vivo tests underlined a good effectiveness of quercetin and curcumin nanovesicles in counteracting TPA (phorbol ester) induced lesions and inflammation. Myeloperoxydase activity, used to gauge inflammation, was markedly inhibited by quercetin liposomes (59%) and curcumin liposomes and PEG-PEVs (∼68%). Histology showed that PEG-PEVs provided an extensive reepithelization of the TPA-damaged skin, with multiple layers of thick epidermis. In conclusion, nanoentrapped polyphenols prevented the formation of skin lesions abrogating the various biochemical processes that cause epithelial loss and skin damage.
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In the present study, curcumin nanoformulation loaded methoxy poly(ethylene glycol)-graft-chitosan film (curcumin-MPEG-chitosan film) was developed and its applicability in the wound healing was investigated. In vitro cytotoxicity test showed that the developed MPEG-chitosan film was non-cytotoxic. Antioxidant efficiency tests revealed that the antioxidant efficiency of curcumin in the film did not show any significant difference compared with that of unmodified curcumin. Furthermore, in vivo wound healing test showed that the rate of wound reduction was greatly elevated with the rapid re-epithelialization in curcumin-MPEG-chitosan film group. Masson's Trichrome staining and the hydroxyproline measurement in the wound tissue also suggested that application of curcumin-MPEG-chitosan film could greatly increase the collagen synthesis compared with that of MPEG-chitosan film treatment. Therefore, all these results proved the effectiveness of curcumin-MPEG-chitosan film in the application of wound healing.
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A biodegradable in situ gel-forming controlled drug delivery system composed of curcumin loaded micelles and thermosensitive hydrogel was prepared and applied for cutaneous wound repair. Curcumin is believed to be a potent antioxidant and anti-inflammatory agent. Due to its high hydrophobicity, curcumin was encapsulated in polymeric micelles (Cur-M) with high drug loading and encapsulation efficiency. Cur-M loaded thermosensitive hydrogel (Cur-M-H) was prepared and applied as wound dressing to enhance the cutaneous wound healing. Cur-M-H was a free-flowing sol at ambient temperature and instantly converted into a non-flowing gel at body temperature. In vitro studies suggested that Cur-M-H exhibited well tissue adhesiveness and could release curcumin in an extended period. Furthermore, linear incision and full-thickness excision wound models were employed to evaluate the in vivo wound healing activity of Cur-M-H. In incision model, Cur-M-H-treated group showed higher tensile strength and thicker epidermis. In excision model, Cur-M-H group exhibited enhancement of wound closure. Besides, in both models, Cur-M-H-treated groups showed higher collagen content, better granulation, higher wound maturity, dramatic decrease in superoxide dismutase, and slight increase in catalase. Histopathologic examination also implied that Cur-M-H could enhance cutaneous wound repair. In conclusion, biodegradable Cur-M-H composite might have great application for wound healing.