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Encapsulation and Sustained Release of Curcumin using Superparamagnetic Silica Reservoirs
Chemistry - A European Journal
Abstract
The formation of magnetic nanocomposites of silica with curcumin in the cetyltrimethylammonium bromide (CTAB) micellar rod in the presence of super-paramagnetic Fe3O4 nanoparticles was demonstrated. It was observed that the high loading of Fe3O4 nanoparticles in the silica carriers might impart high magnetophoretic mobility for targeted delivery. These magnetic carriers provided an alternative method for site-specific delivery of curcumin with the ability to concentrate them on desired cells or organs by an external magnetic field and increase their residence time in the vicinity of the target area. Small-angle X-ray scattering patterns for the samples before magnetic separation exhibited a distinctive Bragg peak corresponding to ordered porous nonmagnetic silica structures. This study provided a simple and strategic route to encapsulate curcumin inside superparamagnetic porous silica particles.
... Consequently, various research efforts were carried out to load curcumin onto nanocarrier to enhance its water solubility, stability and bioavailability. 1,3 Starch nanoparticles have been demonstrated to be promising nanocarriers for various drugs and nutraceutical products as they are composed of a natural polysaccharide that is renewable, biodegradable, low cost, abundantly available and biocompatible with tissue and cells. 4 Previously, our research group has loaded curcumin onto native starch nanoparticles by the in-situ precipitation microemulsion method. ...
... The mass of nanoparticles remained constant after 8 h. The swelling ratio was calculated based on Equation 3: ...
... As time increased, a higher degree of swelling allows greater access for the solution media to the encapsulated drug, therefore promote more the release of curcumin. [1][2][3]7 The initial burst of curcumin released was observed within 2 h to be around 34% at pH 1.2 and 36% at pH 7.4 which brings the cumulative release close in between the two mediums. Despite the initial burst, curcumin continued to be released gradually at pH 7.4. ...
... In order to overcome the above-cited problems, a mesostructured hybrid carrier is here proposed, which joins the advantages of micelles (drug protection and increase of water solubility) with those of amorphous silica (higher stability and possible release of silicon as orthosilicic acid). The same objective has also been attempted by other research groups [17,18]. Kerkhofs et al. for example, synthesized silica capsules that contained micelles of P123, a surfactant able to enclose the anti-inflammatory drug flurbiprofen [17]. ...
... Kerkhofs et al. for example, synthesized silica capsules that contained micelles of P123, a surfactant able to enclose the anti-inflammatory drug flurbiprofen [17]. Also Chin and coworkers [18] synthesized a hybrid material containing hexadecyltrimethylammonium bromide (CTAB) as a surfactant, curcumin, and iron oxide nanoparticles for a targeted drug delivery. However, this last synthesis was carried out in an acidic environment, required a long time (i.e., days) and involved the use of formamide, a toxic reagent [19]. ...
... Finally, it is worth noting that the present synthesis procedure differs from similar works reported in the literature, such as the one by Chin et al. [18] since it was carried out in basic conditions (instead of the acidic ones), required a shorter time (few hours rather than days) and did not imply the use of toxic organic reagents, such as formamide. Figure 2a reports the XRD patterns obtained at small angles for the reference material Meso_SiO 2 and for the one containing curcumin, Meso_SiO 2 _Cur. ...
Curcumin is a natural active principle with antioxidant, antibacterial and anti-inflammatory properties. Its use is limited by a low water solubility and fast degradation rate, which hinder its bioavailability. To overcome this problem, curcumin can be delivered through a carrier, which protects the drug molecule and enhances its pharmacological effects. The present work proposes a simple one-pot sol–gel synthesis to obtain a hybrid carrier for curcumin delivery. The hybrid consists of a mesostructured matrix of amorphous silica, which stabilizes the carrier, and hexadecyltrimethylammonium (CTA), a surfactant where curcumin is dissolved to increase its water solubility. The carrier was characterized in terms of morphology (FESEM), physicochemical properties (XRD, FTIR, UV spectroscopy) and release capability in pseudo-physiological solutions. Results show that curcumin molecules were entrapped, for the first time, in a silica-surfactant mesostructured hybrid carrier. The hybrid carrier successfully released curcumin in artificial sweat and in a phosphate buffer saline solution, so confirming its efficacy in increasing curcumin water solubility. The proposed drug release mechanism relies on the degradation of the carrier, which involves the concurrent release of silicon. This suggests strong potentialities for topical administration applications, since curcumin is effective against many dermal diseases while silicon is beneficial to the skin.
A simple one-pot sol–gel organic-solvent-free synthesis, at room temperature, leads to the formation of a hybrid mesostructured CTA–silica containing curcumin. When in pseudo-physiological solutions, the hybrid releases curcumin (enclosed in surfactant micelles), with enhanced solubility, and silicates. This material is a promising candidate for topical administration of drugs, since curcumin is effective against several dermatological diseases and silicon is beneficial to skin.
... A series of natural and synthetic nanoscale carriers for fluorescent images of biological objects creation and for the usage as medicine transporters has been developed [7]. C 60 -fullerenes [3,4,[7][8][9], nanodiamonds, carbon nanotubes [1,3,5,6,11], nano silicium dioxide [9,15,[17][18][19][20][21][22][23][24][25] occupy an important place for address transport of medicines to target organs. Used nanoparticles should be non-toxic, easily synthesizing or selfassembling and decaying and easily excreting from the body. ...
... Used nanoparticles should be non-toxic, easily synthesizing or selfassembling and decaying and easily excreting from the body. Today, the most promising structures are nanodiamonds, nano silicium dioxide [9,[17][18][19][20][21][22][23][24][25], nanostructures which decompose eventually: poly (L-lysine) [22], poly (lactic-co-glycolic acid) (PLGA) [26,27] and curcumin-based nanoparticles [17][18][19][20][21][22][23][24][25]28] (Fig. 1). These nanostructures are not new objects of study, but now they are quite widely used [1, 9-12, 15, 17-26, 27-30]. ...
... Used nanoparticles should be non-toxic, easily synthesizing or selfassembling and decaying and easily excreting from the body. Today, the most promising structures are nanodiamonds, nano silicium dioxide [9,[17][18][19][20][21][22][23][24][25], nanostructures which decompose eventually: poly (L-lysine) [22], poly (lactic-co-glycolic acid) (PLGA) [26,27] and curcumin-based nanoparticles [17][18][19][20][21][22][23][24][25]28] (Fig. 1). These nanostructures are not new objects of study, but now they are quite widely used [1, 9-12, 15, 17-26, 27-30]. ...
... Recently, curcumin has been studied for its benefits to sports medicine because of its antioxidant and anti-inflammatory potential (Zhao et al., 2015). However, because curcumin is sensitive to alkaline conditions, heat treatment, light, metal ions, enzymes, oxygen, and ascorbic acid, it is often encapsulated to improve solubility, stability, and bioavailability (Chin et al., 2009;Dar et al., 2017;Hatcher et al., 2008). ...
... Curcumin is a lipophilic agent and its own hydrophobic nature makes it insoluble in water (Chin et al., 2009;Shehzad et al., 2017). ...
Spray drying was used to develop two products: whey protein concentrate (WPC) and whey protein concentrate admixture of microencapsulated curcumin (TWPC). We aimed to characterize the concentrate's technological attributes to verify whether lactose remains in an amorphous state even after the addition of turmeric extract containing curcumin, a compound with antioxidant and anti‐inflammatory properties. Analysis of morphology, particle size distribution, Raman spectroscopy, sorption isotherms and colorimetry were carried out. WPC and TWPC showed spherical, irregular, particulate morphology with agglomeration points, without apparent cracks. Differences in the L*, a*, b* values between WPC and TWPC showed that the addition of curcumin extract, which is a natural orange‐yellow dye, has led to a tendency toward yellow coloration. The sorption isotherms indicated no difference in its curved shape. The presence of turmeric extract in TWPC sample modified WPC Raman spectrum. Thus, it was possible to develop TWPC without altering WPC technological characteristics. Whey protein concentrate (WPC) and whey protein concentrate admixture of microencapsulated curcumin (TWPC) showed spherical, irregular, particulate morphology with agglomeration points, without apparent cracks. The differences in the L*, a*, b* values between WPC and TWPC showed that the addition of curcumin extract, which is a natural orange‐yellow dye, has led to a tendency toward yellow coloration. Thus, we developed a TWPC without altering WPC technological characteristics.
... Natural agents, like curcumin, attracted a lot of attention, as antioxidant, anti-inflammatory, antimicrobial and chemotherapeutic agent especially because it is well tolerated even at high dosage (up to 12g/day) [215][216]. Superparamagnetic mesoporous silica is a more stable drug delivery system in comparison with polymeric homologues with a hydrophobic surface which can be easily tuned by functionalization. ...
... Superparamagnetic mesoporous silica is a more stable drug delivery system in comparison with polymeric homologues with a hydrophobic surface which can be easily tuned by functionalization. The synergy of the two anticancer mechanisms (hyperthermia and chemotherapy) along with the low side effects recommends this system in cancer treatment [215]. The presence of the magnetic component can also be exploited due to the possibility of magnetic accumulation of these nanoparticles within the tumor tissue or organ and also, there are a lot of strategies whi ch can be used for ensuring good diagnosis capabilities [175]. ...
By the developmentof new antineoplastic drugs addressed tospecific sites (key to tumor growth), targeted agents, which do not interfere with most normal cells have many advantages like fewer side effects (as personalized treatment), and prolonged survival time of cancer patients compared to conventional therapy. As current approaches in cancer therapy, drug delivery systems based on polymers (synthetic, natural or combinations like micelles, nanospheres, nanocapsules, nanogels, polymer-drug conjugates, polymer-drug polyplex, polymersomes) are more benefic compared to parent free drug, because of targeted effect of delivery, low toxicity, solubility in biological fluids and immunostimulatory effects. Synthetic polymers (polyesters, polyamides and polyethers) are the most used core materials for drug delivery systems, many of them being officially certified. On the other hand due to their better biocompatibility and biodegradability, the natural ones (polysaccharides and proteins) are still a hot topic on cancer therapy as drug delivery and targeting materials. This article reviews the multifunctional materials used in targeting of drugs with polymer based delivery systems as current-day data and key of future applications on cancer therapy. An increasing interest in the last decades returns to the new, engineered inorganic materials as well as to the newly optimized composites and nanocomposites.
... Natural agents, like curcumin, attracted a lot of attention, as antioxidant, anti-inflammatory, antimicrobial and chemotherapeutic agent especially because it is well tolerated even at high dosage (up to 12g/day) [215][216]. Superparamagnetic mesoporous silica is a more stable drug delivery system in comparison with polymeric homologues with a hydrophobic surface which can be easily tuned by functionalization. ...
... Superparamagnetic mesoporous silica is a more stable drug delivery system in comparison with polymeric homologues with a hydrophobic surface which can be easily tuned by functionalization. The synergy of the two anticancer mechanisms (hyperthermia and chemotherapy) along with the low side effects recommends this system in cancer treatment [215]. The presence of the magnetic component can also be exploited due to the possibility of magnetic accumulation of these nanoparticles within the tumor tissue or organ and also, there are a lot of strategies whi ch can be used for ensuring good diagnosis capabilities [175]. ...
By the developmentof new antineoplastic drugs addressed tospecific sites (key to tumor growth), targeted agents, which do not interfere with most normal cells have many advantages like fewer side effects (as personalized treatment), and prolonged survival time of cancer patients compared to conventional therapy. As current approaches in cancer therapy, drug delivery systems based on polymers (synthetic, natural or combinations like micelles, nanospheres, nanocapsules, nanogels, polymer-drug conjugates, polymer-drug polyplex, polymersomes) are more benefic compared to parent free drug, because of targeted effect of delivery, low toxicity, solubility in biological fluids and immunostimulatory effects. Synthetic polymers (polyesters, polyamides and polyethers) are the most used core materials for drug delivery systems, many of them being officially certified. On the other hand due to their better biocompatibility and biodegradability, the natural ones (polysaccharides and proteins) are still a hot topic on cancer therapy as drug delivery and targeting materials. This article reviews the multifunctional materials used in targeting of drugs with polymer based delivery systems as current-day data and key of future applications on cancer therapy. An increasing interest in the last decades returns to the new, engineered inorganic materials as well as to the newly optimized composites and nanocomposites.
... Such systems can be easily manipulated for improved delivery, activity and specificity. Mesoporous silica nanoparticles (MSN) are one of the most employed nanosystems for improving the bioavailability of poorly water soluble drugs99100101102103104105106107. Due to their ordered nanoporous structures, high surface areas, large pore volumes and high surface densities of hydroxyl groups, MSNs can be functionalized easily. ...
... Curcumin binds covalently through a silicon-oxygen bond at the diketo moiety (Figure 2). Curcumin-loaded MSNs have been prepared and employed in several studies99100101102103104105106107. In these systems, curcumin release could be controlled for even up to several hours along with improvement in the stability and bioavailability of curcumin. ...
Curcumin, a pigment from turmeric, is one of the very few promising natural products that has been extensively investigated by researchers from both the biological and chemical point of view. While there are several reviews on the biological and pharmacological effects of curcumin, chemistry reviews are comparatively scarcer. In this article, an overview of different aspects of the unique chemistry research on curcumin will be discussed. These include methods for the extraction from turmeric, laboratory synthesis methods, chemical and photochemical degradation and the chemistry behind its metabolism. Additionally other chemical reactions that have biological relevance like nucleophilic addition reactions, and metal chelation will be discussed. Recent advances in the preparation of new curcumin nanoconjugates with metal and metal oxide nanoparticles will also be mentioned. Directions for future investigations to be undertaken in the chemistry of curcumin have also been suggested.
... The Curcumin-loaded APTES-Fe3O4 and HA NPs were evaluated for their ability to slowly release the substance through testing the leaching of Curcumin in phosphate buffer at the pH of the human body (pH 7. 4), as illustrated in Figures 8b. As time goes on, a noticeable rise was observed in absorbance seen in the UV spectra of the HA NPs and APTES-Fe3O4, both of which are loaded with Curcumin and dissolved in buffer solution (18). However, the sustainability of the release rate decreased significantly when the time was extended. ...
... All these systems demonstrated higher curcumin bioavailability as well as improved water solubility [77,79]. One of the most often used nanosystems for enhancing the bioavailability of herbal medicines with limited water solubility is mesoporous silica nanoparticles (MSN), which include curcumin [80][81][82][83][84]. The biological and medical applications of the gold nanoparticlebased curcumin formulations for drug delivery, cancer treatment, and cancer diagnosis and diagnosis attracted increased attention from the scientific community for their target-specific drug delivery [85][86][87]. ...
Background
Curcumin is a natural compound obtained from Curcuma longa that possesses a vast therapeutic potential for disease treatment. It is a potent anticancer, anti-inflammatory, antioxidant, and anti-aging phytochemical as evident from numerous studies. Curcumin's anti-inflammatory and antioxidant properties are thought to be more potent than its other biological actions. Curcumin's anti-inflammatory properties can lead to an improvement in symptoms and make it a viable candidate for the treatment and prevention of pro-inflammatory disorders.
Objective
The goal of this review is to analyse curcumin's anti-inflammatory properties and mechanisms in the treatment of various disorders. The effect of different curcumin-based nanoformulations on anti-inflammatory potential is also reviewed, as the therapeutic use of curcumin is influenced by its solubility, bioavailability, and pharmacokinetic profile.
Methodology
The literature searched during the last ten years using keywords such as curcumin, anti-inflammatory mechanisms, cytokines, and nanoformulations from multiple databases, such as PubMed, Science Direct, Scopus, and others. The quality research and review articles containing the aforementioned keywords were chosen for this review article.
Conclusion
This review focuses on the anti-inflammatory properties of curcumin against a variety of inflammatory disorders that arise over the course of various illnesses. It also emphasises the importance of developing alternative nanoformulations to address the limitations of curcumin usage. Further, it will aid the scientific community's understanding of curcumin and its anti-inflammatory mechanisms, prompting them to devise innovative treatment options.
... This approach can also be utilized for the delivery of other drugs. [213] A promising new composite material comprising of polystyrene/poly(N-isopropylacrylamide), as a thermoresponsive polymer, and silica nanoparticles in a core-shell morphology was reported for the encapsulation and release of 17-AAG. The composite showed a steady release of 17-AAG at 40°C, above the transition temperature of poly(N-isopropylacrylamide), while no release was observed at 25°C which is below the transition temperature. ...
Prostate cancer (PCa) is one of the most commonly diagnosed cancers and is the fifth common cause of cancer‐related mortality in men. Current methods for PCa treatment are insufficient owing to the challenges related to the non‐specificity, instability and side effects caused by the drugs and therapy agents. These drawbacks can be mitigated by the design of a suitable drug delivery system that can ensure targeted delivery and minimise side effects. Silica based nanoparticles (SBNPs) have emerged as one of the most versatile materials for drug delivery due to their tunable porosities, high surface area and tremendous capacity to load various sizes and chemistry of drugs. This review gives a brief overview of the diagnosis and current treatment strategies for PCa outlining their existing challenges. It critically analyzes the design, development and application of pure, modified and hybrid SBNPs based drug delivery systems in the treatment of PCa, their advantages and limitations.
... To enhance bioavailability, curcumin was encapsulated using superparamagnetic porous silica particles. This simple procedure offered magnetophoretic mobility for the targeted delivery of curcumin [67]. Furthermore, to overcome the short half life of turmeric, bovine serum albumin functionalized silver NPs (SNP: BSA) loaded with curcumin were found to have higher half-life. ...
Background:
The concept of nutraceuticals has gained increased interest recently as it is based on using natural substances for therapeutic applications. However, limitations such as low bioavailability have restricted the use of these substances thus far. Nanoencapsulation of nutraceuticals has been proposed as a promising solution to circumvent such issues by increasing their bioavailability and targeting their release. Metal and metal oxide nanoparticles are amongst the inorganic nanocarriers that have been studied for their ability to encapsulate nutraceuticals.
Objectives:
The aim of this article is to provide an overview of metal and metal oxide nanoparticles and their synthesis and applications. Furthermore, the conjugation of these nanoparticles with nutraceuticals will be discussed along with their potential applications.
Conclusion:
It has been observed that the conjugation of nutraceuticals with metal nanoparticles resulted in the cumulative properties of both these factors with increased effectiveness. Such advancements are crucial for nutraceutical use in important theranostic applications that combine diagnosis and therapy.
... The molar ratio of H 2 O/HCl/formamide/CTABr/tetraethylorthosilicate was 100:7.8:10.2:0.11:0.13. 94 This new synthetic methodology for preparing composite materials is likely to be applicable to other biologically active materials. A study prepared CUR-loaded magnetic nanoparticles with 810/ 300 mg Fe 3+ /Fe 2+ salts, 200 mg cyclodextrin (CD), and 250 mg F127, which could be efficiently internalized into human pancreatic cancer cells and improve mice survival. ...
Curcumin (CUR), as a traditional Chinese medicine monomer extracted from the rhizomes of some plants in Ginkgo and Araceae, has shown a wide range of therapeutic and pharmacological activities such as anti-tumor, anti-inflammatory, anti-oxidation, anti-virus, anti-liver fibrosis, anti-atherosclerosis, and anti-Alzheimer’s disease. However, some issues significantly affect its biological activity, such as low aqueous solubility, physico-chemical instability, poor bioavailability, and low targeting efficacy. In order to further improve its curative effect, numerous efficient drug delivery systems have been carried out. Among them, physicochemical targeting preparations could improve the properties, targeting ability, and biological activity of CUR. Therefore, in this review, CUR carrier systems are discussed that are driven by physicochemical characteristics of the microenvironment (eg, pH variation of tumorous tissues), affected by external influences like magnetic fields and vehicles formulated with thermo-sensitive materials.
... Based on Eq. (1), the calculated curcumin loading on Fe 3 O 4 /SiO 2 -CUR NC was about 23%, (0.46 mg/mL). Loading efficiency greatly depends on the interactions between the SiO 2 and curcumin 25,26 . The drug release profile of the Fe 3 O 4 /SiO 2 -CUR in the absence and presence of NIR was compared with free curcumin (pH = 7.4). ...
Breast cancer is a neoplastic disease with a high mortality rate among women. Recently, photodynamic therapy (PDT) and photothermal therapy (PTT) attracted considerable attention because of their minimal invasiveness. The PTT approach works based on hyperthermia generation, and PDT approach employs laser irradiation to activate a reagent named photosensitizer. Therefore, in the current paper, a dual-functioned nanocomposite (NC) was designed for the treatment of breast cancer model in Balb/c mice with the combination of photodynamic and photothermal approaches. Transmission electron microscopy, UV-visible spectroscopy, FTIR, and XRD were employed to validate the nanostructure and silica coating and curcumin (CUR) immobilization on the Fe 3 O 4 nanoparticles. The effect of Fe 3 O 4 /SiO 2-CUR combined with PDT and PTT was assessed in vivo on the breast tumor mice model, and immunohistochemistry (IHC) was employed to evaluate the expression of apoptotic Bax and Caspase3 proteins. The TEM images, UV-visible absorption, and FTIR spectra demonstrated the successful immobilization of curcumin molecules on the surface of Fe 3 O 4 /SiO 2. Also, MTT assay confirmed the nontoxic nature of Fe 3 O 4 /SiO 2 nanoparticles in vitro. In the breast tumor mice model, we have assessed six treatment groups, including control, CUR + PDT, Blue + NIR (near-infrared) lasers, NC, NC + PTT, and NC + PDT + PTT. The tumor volume in the NC + PDT + PTT group showed a significant reduction compared to other groups (p < 0.05). More interestingly, the tumor volume of NC + PDT + PTT group showed a 27% decrease compared to its initial amount. It should be noted that no detectable weight loss or adverse effects on the vital organs was observed due to the treatments. Additionally, the IHC data represented that the expression of proapoptotic Bax and Caspase3 proteins were significantly higher in the NC + PDT + PTT group compared to the control group, indicative of apoptosis. To conclude, our data supported the fact that the NC + PDT + PTT strategy might hold a promising substitute for chemotherapy for the treatment of triple-negative breast cancers. Breast cancer is one of the deadliest diseases among women, which leads to metastasis to vital organs such as the lungs and bones in the body. Approximately one in eight women is encountered with breast cancer in her lifetime 1,2. Recent studies on cancer treatment try to find the best and the least risky way to replace the old methods. The major problem in the currently employed cancer treatments is their adverse side effects on the healthy tissues. Nowadays, various methods are being used for the treatment of breast cancer, such as surgery, targeted therapy, hormone therapy, radiation therapy, chemotherapy, photodynamic therapy (PDT), and photothermal therapy (PTT) 3. Among these methods, PDT and PTT are valid alternative techniques that recently attracted considerable attention for the treatment of a broad range of diseases, including malignant tumors, because of OPEN
... Natural products such as plant extracts provide a wide range of opportunities for new drug discoveries because of chemical diversity, either as pure compounds or as standardized extracts [23]. Recent evidences suggest that herbal-based products are a precious source for the production of chemical entities that could be utilized for the treatment of some complex diseases [24]. The phytochemicals present in herbal products help in building immunity against microbial infections [25]. ...
Objective: The proposed study is carried out to synthesize and characterize silver nanoparticles (AgNPs) using rhizomes of Asparagus racemosus and to evaluate its antimicrobial activity in vitro. Methods: Aqueous extract of A. racemosus rhizomes was prepared and subjected to preliminary phytochemical screening. AgNPs of A. racemosus rhizomes were prepared using standard procedure. The synthesized particles were characterized using ultraviolet-visible spectrophotometry, Fourier transform infrared (FTIR) spectroscopy, and scanning electron microscopic (SEM) analysis. Further, these nanoparticles were subjected to in vitro antimicrobial studies. Results: Preliminary phytochemical analysis showed the presence of tannins, phlobatannins, saponins, flavonoids, terpenoids, triterpenoids, alkaloids, carbohydrates, proteins, anthraquinones, polyphenols, and glycosides. The study of synthesized AgNPs showed a sharp absorbance at 410 nm. The results of FTIR analysis confirmed the presence of phenol, alkanes, aliphatic amine, secondary alcohol, alkenes, and aromatic amines. SEM analysis of the AgNPs revealed higher density polydispersed AgNPs of various sizes. The AgNPs synthesized from rhizome extract showed higher toxicity toward tested microorganisms when compared to extract alone. Conclusion: It has been concluded that silver nanoparticles of A. racemosus could be a good source of plant-derived antimicrobials.
... Particularly, when normalized to the mass of pure Fe 3 O 4 based on TGA data, FA4 and FA4D exhibit high values of saturation magnetization. Similar phenomena were reported for Fe 3 O 4 nanoparticles coated with different polymeric shells and were explained by the acceleration of magnetic order in the surface of nano-Fe 3 O 4 by coating process [50,51]. Such high value of saturation magnetism of Fe 3 O 4 in FA4 and FA4D suggests that these samples are able to apply in hyperthermia, as discussed below. ...
Chemotherapy in cancer treatment usually leads to serious side effects on patients due to the unselectiveness and high toxicity on normal cells of cancer drugs. Loading cancer drugs into nano-platforms could be an alternative approach to effectively deliver drugs to tumors and reduce toxic exposure on healthy cells. In this work, we synthesized drug delivery nano-systems based on Fe3O4 nanoparticles (obtained from co-precipitation reaction) which could provide targeting of drugs to the tumor sites by an external magnetic field. Also, the magnetic nanoparticles (MNPs) could generate heat to kill cancer cells at a certain temperature range. The systems were designed for loading anticancer agent doxorubicin by using alginate-coated iron oxide MNPs. It was found that the loading was achieved by complex formation of doxorubicin and the alginate layer. Various concentrations of alginate solutions produced different sizes as well as drug loading capacities of the nanoparticles. The highest loading content of 18.96% achieved at the alginate concentration of 4 mg ml⁻¹, corresponding to the mass ratio of alginate to Fe3O4 of around 1:2. The magnetic properties, especially the inductive heating effect of the nanoparticles, along with the impact of the systems on tumor cells were investigated. The results proved that the nanoparticles can serve as a good drug delivery system, in terms of both effective hyperthermia and chemotherapy. © 2018 Springer Science+Business Media, LLC, part of Springer Nature
... and Department of Biosciences, Jamia Millia Islamia, New Delhi, India-110025; E-mail: rizvi_ma@yahoo.com suffered from poor solubility, bioavailability and clinical efficacy [10]. Furthermore, many reviewers' have tried to increase water solubility and bioavailability of curcumin by entrapment of curcumin in biodegradable polymeric nanoparticles. ...
Background:
Curcumin is a potent anticancer agent and has great potential efficacy against different types of cancers. A major disadvantage of curcumin, however, is its poor solubility and bioavailability.
Objective:
The aim of the present work is to synthesize chitosan and curcumin-loaded chitosan nanoparticles and their characterization through various physicochemical methods and cellular uptake in cervical cancer cell line SiHa.
Method:
Chitosan nanoparticles were synthesized through the method of ionic gelation of chitosan with sodium Tripolyphosphate (TPP). In addition, the internal structure of chitosan nanoparticles and curcumin loaded chitosan nanoparticles were characterized by DLS, UV-Visible spectrophotometer, DSC, LCMS and LDH assay.
Results:
The studies presented demonstrate that curcumin-loaded chitosan nanoparticles showed increased uptake in the SiHa cells as compared to free curcumin and chitosan nanoparticles did not show any significant uptake in SiHa cell line. The curcumin-loaded chitosan nanoparticles released more lactate and lower ATP as compared to native curcumin in cervical cancer lines such as SiHa, CaSki and HeLa.
Conclusion:
Thus, chitosan based curcumin nanoparticles could be used as a potent vector / delivery agent for drug targeting in the treatment of cervical cancer.
... Iron-based magnetic nanoparticles (NPs) such as magnetite (Fe 3 O 4 ) have been studied in detail due to their unique properties, such as stability over time, biocompatibility, and sensitivity to magnetic field. [1][2][3] They can potentially be used as magnetic targeted drug delivery carriers and magnetic resonance imaging contrast agents due to their high saturation magnetization, low toxicity, and biocompatibility. 4 The magnetic properties of Fe 3 O 4 NPs are attributed to their size and size distribution, which, in turn, is dependent on the route of synthesis. ...
Over the last decade, there has been growing interest in developing novel nanoparticles (NPs) for biomedical applications. A safe-by-design approach was used in this study to synthesize biocompatible iron oxide NPs. The size of the particles obtained was ~100 nm. Although these NPs were significantly (P<0.05) internalized in MCF-7 (human breast adenocarcinoma cell line) cells, no adverse effect was observed in the cells as assessed by cytotoxicity assays (neutral red uptake and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) and cell cycle analysis. Our data demonstrate the potential of iron oxide NPs as a biocompatible carrier for targeted drug delivery.
... The curcumin-loaded CBs were then removed from the curcumin solution and dried at room temperature. The amount of curcumin incorporated into CBs was determined based on methods reported by Chin et al. [21]. Curcumin-loaded CBs (100 mg) were mechanically crushed into powder form, added into 10.0 mL absolute ethanol, and stirred in darkness at room temperature for 24 h. ...
Highly porous cellulose beads (CBs) of various mean sizes were successfully prepared from regenerated cellulose of paper wastes. The drug delivery characteristics of CBs with different mean sizes were investigated using curcumin as the model drug under controlled conditions. The loading capacity and efficiency of curcumin onto CBs were substantially influenced by factors such as their morphological characteristics, curcumin concentration, and duration of loading. The release kinetic profiles of curcumin from CBs of different mean sizes were investigated in media of pH values resembling digestive juices and intestinal fluids. Release kinetic models were used to simulate and elucidate release kinetics and mechanisms of curcumin from CBs under specific conditions. The loading capacity and efficiency of curcumin onto CBs could be enhanced via the optimization of curcumin solution concentration and the morphological characteristics of CBs, whereas the release kinetic profiles of curcumin from CBs could be modulated by varying the mean diameter of CBs. Optimized CBs derived from regenerated cellulose of paper wastes are potentially useful as cost-effective drug delivery carriers.
... 6 Though silica aerogels have been widely studied as drug delivery carriers, they suffered from drawbacks that include brittleness and non-biodegradability. 7 Because aerogels are biodegradable, renewable, non-toxic, affordable, have favourable surface functionality and are polysaccharide-based (e.g., starch, alginate, chitosan, pectin, cellulose, etc.) aerogels are more favourable drug delivery carriers. 8 Starch and alginate aerogels have been studied as controlled release carriers using paracetamol and ibuprofen as model drugs. The drug loading capacity of these polysaccharide-based aerogels was found to be comparable to silica aerogels. ...
Currently most of the aerogel-based drug delivery carriers are made from non-biodegradable materials, such as silica. In this study, highly porous cellulose aerogels with Brunauer-Emmett-Teller (BET) surface areas that varied between 22 m² g⁻¹ and 525 m² g⁻¹ were prepared from a sugarcane bagasse cellulose solution of various concentrations. The potential utility of cellulose aerogels as controlled release carriers was evaluated by loading methylene blue (MB) as a model hydrophilic drug. The MB loading capacity and release kinetic profiles of cellulose aerogels were observed to be substantially influenced by their BET surface areas. Under optimum conditions, a maximum loading capacity of 6.4 mg MB mg⁻¹ cellulose aerogel was achieved with sustained release of MB from cellulose aerogels at physiological pH over a period of 23 h.
... To improve the low solubility and poor bioavailability, numerous approaches were undertaken by many researchers. Nanoparticle (NP)-based drug delivery [12][13][14][15][16] in which curcumin was encapsulated in liposomes [17], solid lipid microparticles such as chitosan [18], and bovine serum albumin [19]; complexed with phospholipids [20]; or chelated with metals and cyclodextrin [21] has been reported. Micro/ nanoencapsulation techniques have attracted wide attention in the food and pharmaceutical industries for their various applications, including protecting bioactivity and controlled release for improving bioavailability. ...
Curcumin exhibits various biological activities; however, its applications are limited because of its poor water solubility. In this study, we describe an encapsulation process that improves this property using a polyrhodanine shell material synthesized by oxidative polymerization. Unlike the previous methods of oxidative polymerizations, we used the Fenton reaction to introduce a FeCl3/H2O2 combination system. By changing the rhodanine monomer ratio, the curcumin/polyrhodanine nanocapsule (CPR-NC) shell thickness could be controlled. The release behavior of curcumin was characterized by UV–Vis spectroscopy over time. Antimicrobial tests with curcumin, polyrhodanine, and CPR-NC were performed to analyze the minimum inhibitory concentration and inhibition zones.
... 1−8 However, free CCM cannot be administered systemically due to its high hydrophobicity and poor bioavailability. Although various attempts have been made to encapsulate CCM in inorganicbased carriers such as silica 9 NPs or organic-based carriers exampling cyclodextrin, 10 micelles, 11−14 and liposomes 15,16 NPs, etc. to render CCM dispersible in aqueous media, the synthesis process of these NPs was relatively complicated and time-consuming. Therefore, it is highly desired to develop a simple and efficient methodology for the incorporation CCM into nanocarriers. ...
A straightforward nanoprecipitating method was developed to prepare water dispersible curcumin (CCM)-loaded nanoscale zeolitic imidazolate framework-8 (CCM@NZIF-8) nanoparticles (NPs). The as-synthesized CCM@NZIF-8 NPs possess high drug encapsulation efficiency (88.2%), good chemical stability at physiological condition and fast drug release in acidic microenvironments. Confocal laser scanning microscopy and cytotoxicity experiments reveal that NZIF-8 based nanocarriers promote the cellular uptake of CCM and result in higher cytotoxicity of CCM@NZIF-8 than that of free CCM towards HeLa cells. The in vivo anticancer experiments indicate that CCM@NZIF-8 NPs exhibit much higher antitumor efficacy than free CCM. This work highlights the potential of using nanoscale metal organic framworks (NMOFs) as a simple and stable platform for developing highly efficient drug delivery system in cancer treatment.
... Encapsulation represents an available and efficient approach to circumvent this problem. Therefore, curcumin has been encapsulated in nanoparticles (Bisht et al., 2007; Dadhaniya et al., 2011; Kumar, Kasoju, & Bora, 2010), superparamagnetic silica reservoirs (Chin et al., 2009) and ultrathin fibers (Fu et al., 2014). An ultrathin fiber is a one-dimensional flexible nano-element that can be processed by electrospinning (Ramakrishna, Fujihara, Teo, Lim, & Ma, 2005) and it has several advantages over other encapsulation systems such as high surface area per unit volume, high encapsulation efficiency and controlled release characteristics (Hu et al., 2014). ...
... The absorbance of alkaline curcumin aqueous solution measured at the wavelength of 350 nm was observed to increase linearly ( 2 = 0.9978) with curcumin concentration of up to 0.08 mM at 25 ∘ C ( Figure 6). According to some authors [24] symmetrical curcumin molecule absorbed at a wavelength of 360 nm. A shoulder peak was observed at 360 nm for curcumin in basic media [25]. ...
We have demonstrated the loading of curcumin onto starch maleate (SM) under mild conditions by mixing dissolved curcumin and SM nanoparticles separately in absolute ethanol and ethanol/aqueous (40: 60 v/v), respectively. Curcumin-loaded starch-maleate (CurSM) nanoparticles were subsequently precipitated from a homogeneous mixture of these solutions in absolute ethanol based on the solvent exchange method. TEM analysis indicated that the diameters of CurSM nanoparticles were ranged between 30 nm and 110 nm with a mean diameter of 50 nm. The curcumin loading capacity of SM as a function of loading duration was investigated using the UV-visible spectrophotometer. The loading of curcumin onto SM increased rapidly initially with loading duration, and the curcumin loading capacity of 15 mg/g was reached within 12 hours. CurSM nanoparticles exhibited substantially higher water solubility of 6.0 × 10-2 mg/mL which is about 300 times higher than that of pure curcumin. With enhanced water solubility and bioaccessibility of curcumin, the potential utility of CurSM nanoparticles in various biomedical applications is therefore envisaged.
... Nanoparticles manufactured from poly(lactic-co-glycolic acid) (PLGA) (Shaikh et al. 2009;Mukerjee and Vishwanatha, 2009;Anand et al. 2010), superparamagnetic silica reservoirs (Chin et al. 2009), composite nanoparticles from alginate, chitosan, and pluronic (Das et al. 2010), soy protein isolate (Teng et al. 2012), chitosan/ poly(butyl cyanoacrylate) (Duan et al. 2012) have all been studied. Zein nanoparticles made using electrohydrodynamic atomization (Gomez-Estaca et al. 2012), curcumin-HSA nanoparticles using albumin bound nanoparticle technology (Kim et al. 2011), etc., peptide hydrogels (Altunbas et al. 2011), hollow microcapsules and bionanotubes (Manju and Sreenivasan 2011;Sadeghi et al. 2013), multilayer vesicles, tubes, porous structures and organo gels (Koley and Pramanik 2012), and magnetic nanoparticles (Wang et al. 2013) have all been explored in terms of their effectiveness in encapsulating and delivering curcumin. ...
The desolvation method was successfully used to prepare nanoparticles from bovine serum albumin (BSA) using ethanol, acetone, and their mixtures (70:30 and 50:50, respectively). Ethanol and mixtures of ethanol and acetone led to the most spherical nanoparticles, while using pure acetone resulted in a mixture of spherical and rod shape nanoparticle. Acetone was the solvent with higher encapsulation efficiency equal to 99.2 ± 0.36 %. The polydispersity values of BSA NPs in this study were 0.045 ± 0.007, 0.065 ± 0.013, 0.091 ± 0.012, and 0.120 ± 0.016 for ethanol (100) 4×, Et:Ac (70:30) 4×, Et:Ac (50:50) 4×, and acetone (100) 3×, respectively. Encapsulation efficiencies of curcumin inside BSA NPs were 19.4 ± 2.2 and 19.8 ± 1.6 % for 1.0 and 1.5 molar ratios of curcumin to BSA, respectively. Crosslinking using glutaraldehyde improved the stability of BSA NPs and curcumin-loaded BSA NPs and both groups of nanoparticles were stable for 1 month; the lyophilized curcumin-loaded BSA NPs were able to redisperse in water. The particle size and polydispersity index of redispersed NPs were higher than the original NPs before lyophilization. The size distribution study shows that after 10 s of sonication most nanoparticles were well dispersed; however, a small but significant fraction formed aggregates. Sonication for 10 s decreased the effective diameter and polydispersity of the redispersed nanoparticles, while increasing the sonication time to 20 s did not show significant changes. In vitro release study of curcumin from BSA NPs showed that these biocompatible nanoparticles have the ability to be used as a carrier to improve controlled release of curcumin.
... More recently, curcumin has shown to have antitumor effects in many cancer cell lines [3,4] and the clinical effects of curcumin are being studied in human clinical trials and animal models on various conditions and numerous myeloma [5][6][7]. Despite these promising biomedical properties, free curcumin molecules suffered from low water solubility, which in turn have resulted in poor bioavailability and clinical efficacy [8]. Hence, researchers have attempted to enhance water solubility and bioavailability of curcumin by loading of curcumin in biodegradable polymeric nanoparticles. ...
Curcumin was loaded onto starch nanoparticles by using in situ nanoprecipitation method and water-in-oil microemulsion system. Curcumin loaded starch nanoparticles exhibited enhanced solubility in aqueous solution as compared to free curcumin. Effects of formulation parameters such as types of reaction medium, types of surfactant, surfactant concentrations, oil/ethanol ratios, loading time, and initial curcumin concentration were found to affect the particle size and loading efficiency (LF) of the curcumin loaded starch nanoparticles. Under optimum conditions, curcumin loaded starch nanoparticles with mean particles size of 87 nm and maximum loading efficiency of 78% were achieved. Curcumin was observed to release out from starch nanoparticles in a sustained way under physiological pH over a period of 10 days.
... All the hybrids materials demonstrated to have good antioxidant capacity [164]. As ferrite NPs toxicity is not well-defined another study in which curcumin was immobilized in the channels of the SiO 2 mesopores as capping agent was performed [165] Fig. (3). UV/Vis spectroscopy and confocal laser scanning microscopy were used to confirm the presence of curcumin in the final drug nanocarrier. ...
The efficacy, cellular uptake and specific transport of dietary antioxidants to target organs, tissues and cells remains the most important setback for their application in the treatment of oxidative-stress related disorders and in particular in neurodegenerative diseases, as brain targeting remains a still unsolved challenge. Nanotechnology based delivery systems can be a solution for the above mentioned problems, specifically in the case of targeting dietary antioxidants with neuroprotective activity. Nanotechnology-based delivery systems can protect antioxidants from degradation, improve their physicochemical drug-like properties and in turn their bioavailability. The impact of nanomedicine in the improvement of the performance of dietary antioxidants, as protective agents in oxidative-stress events, specifically through the use of drug delivery systems, is highlighted in this review as well as the type of nanomaterials regularly used for drug delivery purposes. From the data one can conclude that the research combining (dietary) antioxidants and nanotechnology, namely as a therapeutic solution for neurodegenerative diseases, is still in a very early stage. So, a huge research area remains to be explored that hopefully will yield new and effective neuroprotective therapeutic agents in a foreseeable future.
In this work, we focused on the two neurodegenerative disorders most frequently seen: Alzheimer’s disease and Parkinson’s disease. Both of their pathophysiologies are discussed. There are various diagnostic and treatment modalities accessible in the medical field. Due to the limitations of conventional medications in treating these terminal diseases, researchers have turned to alternative medicines like curcumin to address side effects and lower treatment costs. However, curcumin has several restrictions that can be removed with nanotechnology. It describes how various nanotechnological techniques can be utilized to improve curcumin as a medication. Lastly, the future aspects and challenges of using curcumin are briefly discussed.
Zeolitic imidazole frameworks are emerging materials and have been considered an efficient platform for biomedical applications. The present study highlights the simple fabrication of methyl gallate encapsulated folate-ZIF-L nanoframeworks (MG@Folate ZIF-L) by a simple synthesis. The nanoframeworks were characterized by different sophisticated instruments. In addition, the drug-
releasing mechanism was evidenced by in vitro releasing kinetics at various pH conditions. The anti-biofilm potential confirmed by the biofilm architectural deformations against human infectious pathogens MRSA and N7 clinical strains. Furthermore, anticancer efficacy assessed against A549 lung cancer cells. The result reveals that the MG@Folate ZIF-L exposed a superior cytotoxic effect due to the pH responsive and receptor-based drug-releasing mechanism. Based on the unique physicochemical and biological characteristics of nanoframeworks, it has overcome the problems of undesired side effects and uncontrolled drug release of existing drug delivery systems. Finally, the in vitro toxicity effect of MG@Folate ZIF-L was tested against the Artemia salina (A. salina) model
organism, and the results show enhanced biocompatibility. Overall, the study suggested that the
novel MG@Folate ZIF-L nanoframeworks is a suitable material for biomedical applications. It will be very helpful to the future design for targeted drug delivery systems.
Sepsis is a life-threatening disease caused by the dis-functioning of the immune response to pathogenic infections. Despite, the discovery of modern therapeutics and treatments of sepsis are lacking due to the resistance of pathogens. Metronidazole is an antibiotic commonly used to treat bacterial infections, but usage is limited and challenging by a short half-life period. In this research work, fabricate a pH-responsive drug delivery system for controlled release of metronidazole targeted molecules. We exemplified that, the encapsulation of hydrophilic metronidazole drug within a hydrophobic ZIF-90 framework can be enhanced the pH-responsive drug release under acidic conditions. The ZIF-90 frameworks only decompose in under acidic solutions, they are highly stable in physiological conditions. The pH-responsive protonation mechanism of ZIF-90 frameworks promotes the quick release of metronidazole within cells. The antimicrobial proficiency of zinc and metronidazole will expose a synergistic effect in ROS-mediated bacterial inhibition and auto-immunity boosting of normal cells. In vitro, antibacterial activity results revealed that the MI@ZIF-90 nano drug delivery system effectively eradicated human infectious pathogens at the lowest concentrations. In anti-fungal activity, studies show excellent growth inhibition against human pathogenic fungi Aspergillus fumigatus and Candida albicans. Finally, the PBMC cytocompatibility study concludes, that the fabricated MI@ZIF-90 drug delivery system is non-toxic to biomedical applications. The overall research findings highlight the design of a smart drug delivery system for sepsis treatment. In future it will be an efficient, low-cost, and biocompatible pharmaceutics for pediatric sepsis management processes.
IntroductionSuper-paramagnetic iron oxide nanoparticles (SPIONs) are known as promising theranostic nano-drug carriers with magnetic resonance imaging (MRI) properties. Applying the herbaceous components with cytotoxic effects as cargos can suggest a new approach in the field of cancer-therapy. In this study mesoporous silica coated SPIONs (mSiO2@SPIONs) containing curcumin (CUR) and silymarin (SIL) were prepared and evaluated on breast cancer cell line, MCF-7.Methods
Nanoparticles (NPs) were formulated by reverse microemulsion method and characterized by DLS, SEM and VSM. The in vitro drug release, cellular cytotoxicity, and MRI properties of NPs were determined as well. The cellular uptake of NPs by MCF-7 cells was investigated through LysoTracker Red staining using confocal microscopy.ResultsThe MTT results showed that the IC50 of CUR + SIL loaded mSiO2@SPIONs was reduced about 50% in comparison with that of the free drug mixture. The NPs indicated proper MRI features and cellular uptake through endocytosis.Conclusion
In conclusion the prepared formulation may offer a novel theranostic system for breast cancer researches.Graphical abstract
In this chapter we review relativistic quantum chemical and molecular dynamics techniques focused on drug discovery and predictive toxicology pertinent to bioinorganic compounds and chelates. We consider transition metal complexes of interest for therapeutic interventions of Alzheimer’s disease and several forms of cancer, especially ovarian and breast cancers. Hence transition metal complexes of curcumin, several analogs of cisplatin, and other second and third row transition metal complexes are highlighted as candidates for treating such diseases and in computer aided drug discovery. Next we have demonstrated the utility of relativistic quantum chemical tools for the studies of lanthanide complexes such as Gd(III) complexes with a number of multidentate ligands which are candidates for highly contrasting agents in MRI and Ce(III)/Eu(III)/Sm(III) complexes as a promising novel line of drugs for tuberculosis. We have also considered a variety of actinide complexes of interest in predictive toxicology and environmental bioremediation elucidating detailed mechanisms of interactions of uranyl and plutonyl ions with human serum protein transferrin and related microbial complexes of actinides exemplifying the significance of such relativistic techniques, especially in the context of medicinal chemistry and drug discovery involving the interactions of actinides with proteins and cells. We have not only reviewed relativistic quantum techniques but also hybrid computational techniques such as QM/MM ONIOM methods, quantum chemical optimization of geometries complexes, and hybrid quantum molecular dynamics methods for providing insights into protein–metal complex/chelate interactions. It is shown that one needs to consider multiple site or allosteric binding approaches to drug discovery in conjunction with relativistic quantum chemical studies even if they are carried out at relatively lower levels such as relativistic effective core potentials combined with density functional level of theory.
We generated stable amphiphilic copolymer-based polymeric micelles (PMs) with temperature-responsive properties utilizing Pluronic® L35 and a variety of ionic liquids (ILs) to generate different aqueous two-phase micellar systems (ATPMSs). The partitioning of the hydrophobic model compound curcumin (CCM) into the PM-rich phase and the drug delivery capabilities of the PMs were investigated. ATPMSs formed using more hydrophobic ILs (i.e., [Ch][Hex] > [Ch][But] > [Ch][Pro] > [Ch][Ac] [Ch]Cl) were the most effective in partitioning (KCCM) and recovering (RECRich) CCM into the PM-rich phase (15.2 < KCCM < 22.0 and 90% < RECRich < 95%, respectively). Moreover, using 1.2 M [Ch][But] and 0.2 M [Ch][Hex] ILs yielded higher encapsulation efficiency (EE) (94.1 and 96.0%, respectively) and drug loading (DL) (14.8 and 16.2%, respectively) values, together with an increase in the average hydrodynamic diameter of the PMs (DH) (42.5 and 45.6 nm, respectively). The CCM-PMs formulations were stable at 4.0, 25.0, and 37.0°C and the release of CCM was faster for the less hydrophobic ILs (i.e., [Ch]Cl and [Ch][Ac]). Furthermore, due to the lower critical solution temperature properties of Pluronic® L35, the PMs exhibit temperature responsiveness at 37.0°C. In vitro cytotoxicity assays were also performed to determine the potency of CCM-PMs formulations, and a 1.8-fold decrease in IC50 values were observed between the CCM-PMs/[Ch][Hex] and CCM-PMs/[Ch]Cl formulations for PC3 cells. The lower IC50 value for the [Ch][Hex] version corresponded to a greater potency compared to the [Ch]Cl version, since a lower concentration of CCM was required to achieve the same therapeutic effect. The ATPMSs investigated in this study serves as a novel platform for Pluronic® L35/buffer PBS (pH 7.4) + IL-based ATPMS development. The unique properties reported here may be useful in applications such as controlled-release drug delivery systems (DDS), encapsulation, and bioseparations.
Curcumin (CCM) is a polyphenolic compound originating from the rhizome of Curcuma longa. In addition to its conventional use as food flavoring, CCM exhibits a high cytotoxic activity against a wide range of tumor cells. However, CCM has poor bioavailability due to its hydrophobic nature. In this study, nanoscale oil bodies (NOBs) were explored for the formulation of CCM. The one-step assembly of NOBs was carried out with CCM, plant oil, phospholipids, and the fusion protein consisting of oleosin and the anti-HER2/neu affibody. NOBs displayed the high encapsulation efficiency of and loading capacity of CCM. Moreover, it resulted in a strong anti-proliferative effect on HER2/neu-positive tumor cells which were administrated with the CCM-loaded NOBs. The result indicates the potential application of NOBs for targeted delivery of CCM.
Bacteria-mediated infectious diseases have become a healthcare challenge globally since the development of antibiotic resistance. Reactive oxygen species (ROS) produced by photosensitizer have great potential in fighting bacterial infections, especially against Gram-negative bacteria that are hard to kill by regular methods owing to its formidable defensive membrane structure under the premise of avoiding overuse of antibiotics. In this work, a small molecular photosensitizer, curcumin (CCM), was used as a model and encapsulated into a zeolitic imidazolate framework-8 (ZIF-8). Then the ZIF-8 loaded with CCM ([email protected]) was decorated with biocompatible polymers hyaluronic acid (HA) and chitosan (CS) by the layer-by-layer self-assembly technique, which results in an antibacterial [email protected]@[email protected] nanoparticle with a high local positive charge density and is to be bind onto the surface of bacteria by electrostatic interaction. The CCM drug loading capability of the nanoparticle was found to be as high as 10.89 %. Upon exposure to blue light (72 J cm−2) for 10 min, the minimum inhibitory concentrations and minimum bactericidal concentrations of [email protected]@[email protected] against Gram-positive bacteria (G(+)) Staphylococcus aureus (S. aureus) and Gram-negative bacteria (G(-)) Escherichia coli (E. coli) were as low as 0.625 and 2.5 μg/mL, respectively, showing highly effective antibacterial activity. After treatment with [email protected]@[email protected] under blue light irradiation, the membranes of S. aureus and E. coli were folded and cracked. Importantly, the antibacterial agent showed good biocompatibility in cytotoxicity test using L929 cells and hemolysis test using rabbit blood cells under blue light irradiation. Therefore, this [email protected]@[email protected] nanocomposite is expected to have great latent capacity in the treatment of superficial traumatic and refractory chronic infections caused by G(+) and G(-).
Rheumatoid arthritis (RA) is an autoimmune disease and characterized by the excessive cell proliferation, abnormal cell cycle of lymphocytes and synovial cells. The therapeutic effects of curcumin in active RA patients were reported, but limited by its insolubility and rapid systemic elimination. Dimethyl curcumin (DiMC) is a metabolically stable analogue of curcum with anti-inflammatory property. In this study, liposomes encapsulated dimethyl curcumin (Lipo-DiMC) was prepared to improve the bioavailability and metabolic-stability; collagen induced arthritis (CIA) rat model was employed to investigate the effects of Lipo-DiMC treatments during CIA progress. Physical assessments and routine-blood-test were performed. Fresh spleen lymphocytes were isolated from normal, CIA and Lipo-DiMC-treated CIA rats; flow-cytometry for cell-cycle analysis, western-blotting for intracellular signal pathway protein expressions, gelatin-zymography for matrix-metalloproteases 2/9 (MMP-2/9) and GF-AFC for dipeptidyl-peptidase I (DPPI) activity assay.
Compared with untreated CIA rats, Lipo-DiMC treatments relieved paw-swellings, suppressed the increments of immunocytes numbers and inhibited DPPI and MMP-2/9 over-activity in blood. Lipo-DiMC adjusted CIA-induced cell cycle dysfunction at G0/G1-phase and S-phase of spleen lymphocytes for CIA rats. The intracellular expression-trends of P38, P21, Bcl-2, JNK-1 and DPPI of spleen lymphocytes were observed during CIA progress with and without Lipo-DiMC administrations. Lipo-DiMC exhibited its therapeutic functions by attenuating CIA development in rats, associated with down-regulating CIA-induced lymphocytes numbers, inhibiting over-expressed of DPPI and MMP-2/9, and adjusting cell cycles. These findings provide a new insight into the mechanism of Lipo-DiMC treatment in CIA rat model and suggest that Lipo-DiMC could be considered as a potential drug for RA treatment.
Highly water-dispersible surfactant-stabilized Fe3O4 magnetic nanocarriers (SMNCs) were prepared by self-assembly of anionic surfactant, sodium dodecyl sulphate (SDS) on hydrophobic (oleic acid coated) nanoparticles and their biomedical applications were investigated. These nanocarriers have an average size of about 10nm and possess tunable surface charge properties. The formation of an organic coating of SDS was evident from infrared spectroscopy, dynamic light scattering, zeta-potential and thermogravimetric measurements. These nanocarriers were used for loading of both hydrophilic and hydrophobic anticancer agents such as doxorubicin hydrochloride (DOX) and curcumin (CUR), respectively. DOX was conjugated onto the surface of nanocarriers through electrostatic interaction, whereas CUR was encapsulated into the hydrophobic interlayer between oleic acid and SDS. The toxicity and cellular internalization of drug loaded nanocarriers were investigated against WEHI-164 cancer cell line. Specifically, the drug loading, pH sensitive drug release and cellular internalization studies suggested that these nanocarriers are suitable for dual drug delivery. Furthermore, they show good heating ability under AC magnetic field, thus can be used as effective heating source for hyperthermia treatment of cancer.
In a new approach, a series of nanoporous non-crystalline alumina (NPA) materials was designed and developed by an evaporation-induced self-assembly method in the presence of various weight percentages of tetrabutylammonium bromide (Bu4N⁺Br⁻) versus P123 (0, 24, 30, 56 and 100) as the dual structure-directing agents. The effect of different amounts of Bu4N⁺Br⁻ on the morphology, pore sizes, and surface area of the samples was carefully monitored. The samples were characterized by N2 adsorption–desorption isotherms, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM) and zeta potential instrumentational methods. The obtained samples have relatively high surface areas (up to 415 m² g⁻¹), great pore volumes (up to 2.00 cm³ g⁻¹) and large pore sizes (up to 23.0 nm). The results indicated that higher pore volume (2.00 cm³ g⁻¹) was obtained when only tetrabutylammonium bromide (namely NPA-100) was used than when only P123 namely NPA-0 (0.5 cm³ g⁻¹) was used as a template. These new supports were used, for the first time, as an inorganic host for poorly soluble guest of curcumin (CUR). XRD analysis confirmed the amorphous state of CUR after being loaded into the NPAs, which is indicative of the full dispersion of the drug into the pores. The in vitro release behavior of these compounds was studied in simulated gastric fluid (SGF, pH = 1.2) and simulated intestinal fluid (SIF, pH = 6.8). The result indicated that the release of insoluble curcumin reached 80% in SGF when it was supported on alumina with ultrahigh pore volume. Moreover, this carrier showed high drug adsorption. The potential of the NPA-100@CUR in protecting SH-SY5Y cells from oxidative stress by toxin 6-OHDA that caused parkinsonian was tested. The results indicated that the formulation neutralizes 6-OHDA toxicity and significantly enhances cell survival.
In the present studies, modified NiO nanoparticles and MnO2/NiO nanocomposites with guanidine were synthesized by anchoring method for carriers of anticancer drug “Caffeic acid phenethyl ester”. The prepared nanocomposites were characterized by using Scanning Electron Microscopy, Raman and Fourier transform infrared spectroscopy, X-ray diffraction, Vibrating sample magnetometer. The results from XRD indicated that the crystalline size of NiO nanoparticles and MnO2/NiO nanocomposites are 12 and 15 nm, respectively. Saturation magnetization (Ms) for NiO NPs and MnO2/NiO nanocomposites was to be 0.60, and 0.68 emu/g indicating that these are superparamagnetic and ferromagnetic properties in nature. The prepared nanocomposites were evaluated as catalyst for degradation of antibiotics in photocatalysis process. Particularly, the MnO2/NiO composite demonstrated the higher degradation rate (89.55%) of tetracycline antibiotic under UV light irradiation than the NiO (67.80%). Drug load on and release from nanopowders was investigated by using UV–Vis spectroscopy method. Time of drug loading was 100 min and the drug release in 1–10 h with 20–80% drug release were found, and then, it's applicable to in-vivo drug delivery. Therefore, the NiO nanoparticles and MnO2/NiO nanocomposites are promising for targeted Caffeic acid phenethyl ester anticancer drug delivery applications. The anticancer drug loaded on guanidine-NiO and guanidine-MnO2/NiO in high concentration has an antioxidant property.
Cancer is the uncontrolled growth of cells in the body and is considered as one of the major causes of death globally. There are several cytotoxic chemotherapeutic agents used to treat cancer including methotrexate, 5-fluorouracil, cisplatin, tamoxifen, doxorubicin and others. Although billions of dollars have been spent on cancer research to develop these chemotherapies, it still remains a major illness for mankind partly due to the shortcomings of these therapies. These shortcomings include low targeting specificity, severe side effects (due to high doses) and poor pharmacokinetics. To avoid these drawbacks, anti-cancer drug delivery systems have been developed recently using nanocarriers including liposomes, micelles, polyelectrolyte capsules and others. One of the recent class of nanoparticles investigated for chemotherapeutic use are metal organic frameworks (MOFs) which are hybrid polymers that consist of metal ions or clusters and organic ligands. MOFs are used in many applications including gas/vapor separation, gas storage, catalysis, luminescent materials, and biomedical imaging. These structures have additional features that promote their use as drug carriers in the biomedical field. First, they are nontoxic, biodegradable and have the ability to carry high loadings of the anti-neoplastic agent due to their porous nature. Also, they have well-defined crystalline structures that can be characterized by different analytical techniques and their sizes are suitable to control their in vivo drug release.
Cancer is the uncontrolled growth of cells in the body and is considered as one of the major causes of death globally. There are several cytotoxic chemotherapeutic agents used to treat cancer including methotrexate, 5-fluorouracil, cisplatin, tamoxifen, doxorubicin and others. Although billions of dollars have been spent on cancer research to develop these chemotherapies, it still remains a major illness for mankind partly due to the shortcomings of these therapies. These shortcomings include low targeting specificity, severe side effects (due to high doses) and poor pharmacokinetics. To avoid these drawbacks, anti-cancer drug delivery systems have been developed recently using nanocarriers including liposomes, micelles, polyelectrolyte capsules and others. One of the recent class of nanoparticles investigated for chemotherapeutic use are metal organic frameworks (MOFs) which are hybrid polymers that consist of metal ions or clusters and organic ligands. MOFs are used in many applications including gas/vapor separation, gas storage, catalysis, luminescent materials, and biomedical imaging. These structures have additional features that promote their use as drug carriers in the biomedical field. First, they are nontoxic, biodegradable and have the ability to carry high loadings of the anti-neoplastic agent due to their porous nature. Also, they have well-defined crystalline structures that can be characterized by different analytical techniques and their sizes are suitable to control their in vivo drug release. This paper reviews the methods used to synthesize MOFs and their recent use as anti-neoplastic drug delivery carriers.
Cancer is one of the most devastating diseases with more than 10 million new annual cases globally. Nutraceuticals are alternative potent therapeutic agents used for the prevention and treatment of various diseases including cancer. Nutraceuticals possessing anticancer activity include, for instance, curcumin, propolis, green tea, silymarin, and capascin. Despite the extraordinary anticancer activity of many nutraceuticals, their clinical use is very limited due to their poor solubility and short half-lives. The recent advances in nanotechnology have showed a revolutionary impact on different aspects of science, especially biomedical science. For instance, nanomaterials-based carrier systems have demonstrated a great potential in incorporating natural products and solving their inherent problems without compromising their therapeutic activities. Moreover, the enhanced permeability and retention (EPR) effect of tumors supported the controlled and targeted delivery of the nanomaterials-loaded nutraceuticals. This chapter outlines the medical importance with an emphasis on anticancer activity of different nutraceuticals. The potential of nanotechnology and nanomaterials in the controlled delivery of nutraceuticals for prevention and treatment of cancer is also discussed.
Polysaccharide-based nanoparticles have been developed as drug delivery nanocarriers for encapsulating and releasing optimum doses of drug at targeted sites over a predictable period of time. We have reported herein the successful loading of curcumin onto both native starch and starch-maleate nanoparticles prepared via in-situ nanoprecipitation in aqueous medium and water-in-oil emulsion, respectively. The physico-chemical characteristics of curcumin-loaded polysaccharide-based nanoparticles such as sizes, porosity, and hydrophilicity or hydrophobicity were subsequently optimized by tailoring synthesis parameters which include solvents, surfactants, cross-linkers, and polysaccharide precursors. Under optimum conditions, native starch nanoparticles with a mean diameter of 87 nm exhibited a maximum curcumin loading efficiency of 78%. Curcumin was observed to release from native starch nanoparticles at physiological pH in sustained and predictable manners over a period of 10 days. On the other hand, the diameter of curcumin-loaded starch-maleate nanoparticles varied between 30 nm and 110 nm and a mean diameter of 50 nm. The loading of curcumin onto starch-maleate nanoparticles occurred rapidly initially but declined gradually until the curcumin loading capacity of 15 mg/g was achieved within 12 hours. Curcumin-loaded starch-maleate nanoparticles exhibited a water solubility of 6.0 x 10-2 mg/mL, which was about 300 times higher than that of free curcumin. Increased water solubility coupled with desirable loading capacity and release kinetic profile of curcumin in polysaccharide-based nanoparticles should, in turn, lead to enhanced bioavailability of curcumin. The potential utility of native starch and starch-maleate nanoparticles as cost-effective polysaccharide-based drug delivery nanocarriers is therefore envisaged.
Stable colloidal suspension of magnetite/starch nanocomposite was prepared by a facile and aqueous-based chemical precipitation method. Magnetite/carbon nanocomposite thin films were subsequently formed upon carbonization of the starch component by heat treatment under controlled conditions. The initial content of native sago starch as the carbon source was found to affect the microstructure and electrochemical properties of the resulted magnetite/carbon nanocomposite thin films. A specific capacitance of 124 F/g was achieved for the magnetite/carbon nanocomposite thin films as compared to that of 82 F/g for pure magnetite thin films in Na2SO4 aqueous electrolyte.
Fine combination of natural botanical extracts to evaluate and maximize their medicinal efficacy has been studied for long. However, their limited shelf-life, complicated extraction protocols, and difficult compositional analysis have always been a problem. It is due to this that such
materials take time to convert them into a proper pharmaceutical technology or product. In this context, we report on synthesis of self-assembled template of one of the most popular natural product, aloevera. This forms a fine porous membrane like structure, in which a natural drug,
Curcumin has been immobilized/trapped. The so-made curcumin-loaded-aloevera (CLA) structures have been carefully evaluated using Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), atomic force microscopy (AFM), UV-vis spectroscopy and fluorescence
microscopy. While FTIR shows that there is no chemical interaction between aloevera and Curcumin, the pores are finely occupied by Curcumin molecules. Fine microscopy structures reveal their distribution and fluorescence microscopy confirm the presence of Curcumin within
the pores. TGA shows 15% loading of the Curcumin in the template and UV-visible spectroscopy data shows independent peaks of both, aloevera (196 nm and 256 nm) and Curcumin (423 nm), respectively. When subjected to antioxidant studies, using DPPH assays, CLAs show a synergistically
superior DPPH radical scavenging activity as compared to only Curcumin and only aloevera extract. Same is true for hydroxyl and NO2 radicals. Trans-membrane release study reveals that there is no significant difference in the amount of Curcumin release from CLAs till
initial 30 min, however, it increases steadily thereafter. CLA is found to facilitate efficient release of Curcumin in 5 h, which is higher as compared to the Curcumin alone.
Magnetite (Fe 3 O 4) nanoparticles with controllable size and shape were synthesized by the thermal decomposition method. In contrast to previously reported thermal decomposition methods, our synthesis method had utilized a much cheaper and less toxic iron precursor, iron acetylacetonate (Fe(acac) 3), and environmentally benign and non-toxic polyethylene oxide (PEO) was being used as the solvent and surfactant simultaneously. Fe 3 O 4 nanoparticles of controllable size and shape were prepared by manipulating the synthesis parameters such as precursor concentrations, reaction durations and surfactants.
Silicalization of curcumin-loaded solid lipid nanoparticles (SLN)/micelles dispersions afforded a compartmentalized nanovector, with both macro and mesostructured domains. SLN act as a reservoir of curcumin (CU), while mesopores are acting as pathway to control drug release. Moreover, the release sustainability depends on the nature of the solid lipid (cetyl palmitate vs stearic acid) and on the pH of the receiving phase. Meso-macrostructrued silica matrix templated by SLN appears thus as promising drug delivery system for pH-responsive controlled release.
The 3-aminopropyltriethoxy silane (APTES) coated magnetite nanopowders were prepared as carriers for anticancer drug "Curcumin" through the modified controlled chemical co-precipitation method using Oleic acid as the apt surfactant to attain ultrafine, nearly spherical and well-dispersed Fe3O4 magnetic nanoparticles. The APTES coated and uncoated Fe3O4 nanoparticles were characterized by XRD, FE-SEM, FT-IR, Raman and VSM techniques. The size of the Fe3O4 nanoparticles and their distribution were determined by particle size analyzer. TEM results show that the average particle size is 15 nm and the particles are homogeneously dispersed which is corroborating well with the FE-SEM images. The room temperature VSM measurements showed that magnetic particles were superparamagnetic characteristics. The amount of APTES bound to the iron oxide nanoparticles were estimated by thermogravimetric analysis (TGA) and the bonding of APTES to the iron oxide nanoparticles was confirmed by FT-IR and Raman analysis. Drug loading and release profile was studied through UV-Vis Spectrophotometer. The curcumin drug binding on to the amino moiety of APTES-Fe3O4 nanoparticle was also confirmed through CLSM and FT-IR spectroscopic techniques. Rapid curcumin drug loading in 2 h and the controlled drug release in 1 h-15% and in 48 h-80% drug release were observed, which is applicable to in-vivo applications. The present findings show that the APTES-Fe3O4 nanoparticles are promising for targeted curcumin drug delivery applications.
Poor water solubility is believed one of the most critical problems of numerous promising pharmaceutical ingredients in their successful clinical utilization. Nanomedicine holds considerable promise to address this challenge, since it extends the therapeutic window of hydrophobic drugs through nanonization approach. Recently, the integration of diagnostic agents with smart therapeutic nanocarriers is also an emerging research arena to simultaneously visualize diseased tissues, achieve site specific drug release and track the impact of therapy. In this study, we have developed a biocompatible smart theranostic nanosystem which transports a highly promising hydrophobic drug (curcumin) in response to mildly acidic environment. As calcium is a main constituent of human body, hence we exploited the reversible calcium chelate formation tendency of divalent calcium to load and unload curcumin molecules. Moreover, an emerging T1 contrast agent is also tethered onto the surface of nanocarrier to realize MRI diagnosis application. In-vitro cell experiments revealed a significantly high chemotherapeutic efficiency of curcumin nanoformulation (IC50; 1.67 μg/mL), whereas free curcumin was found ineffective at the corresponding concentration (IC50; 29.72 μg/mL). MR imaging test also validated the performance of resulting system. Our strategy can be extended for the targeted delivery of other hydrophobic pharmaceutical ingredients.
The utility of mesoporous silica particles to encapsulate nutraceuticals and thereby serve as a molecular tracker, a drugcarrier and a controlled drug release system is investigated.
Curcumin (diferuloylmethane) is a polyphenol derived from the plant Curcuma longa, commonly called turmeric. Extensive research over the last 50 years has indicated this polyphenol can both prevent and treat cancer. The anticancer potential of curcumin stems from its ability to suppress proliferation of a wide variety of tumor cells, down-regulate transcription factors NF-kappa B, AP-1 and Egr-1; down-regulate the expression of COX2, LOX, NOS, MMP-9, uPA, TNF, chemokines, cell surface adhesion molecules and cyclin D1; down-regulate growth factor receptors (such as EGFR and HER2); and inhibit the activity of c-Jun N-terminal kinase, protein tyrosine kinases and protein serine/threonine kinases. In several systems, curcumin has been described as a potent antioxidant and anti-inflammatory agent. Evidence has also been presented to suggest that curcumin can suppress tumor initiation, promotion and metastasis. Pharmacologically, curcumin has been found to be safe. Human clinical trials indicated no dose-limiting toxicity when administered at doses up to 10 g/day. All of these studies suggest that curcumin has enormous potential in the prevention and therapy of cancer. The current review describes in detail the data supporting these studies.
The role of curcumin (diferuloylmethane), a proapoptotic compound, for the treatment of cancer has been an area of growing interest. Curcumin in its free form is poorly absorbed in the gastrointestinal tract and therefore may be limited in its clinical efficacy. Liposome encapsulation of this compound would allow systemic administration. The current study evaluated the preclinical antitumor activity of liposomal curcumin in colorectal cancer. We also compared the efficacy of liposomal curcumin with oxaliplatin, a standard chemotherapy for this malignancy. In vitro treatment with liposomal curcumin induced a dose-dependent growth inhibition [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt] and apoptosis [poly(ADP-ribose) polymerase] in the two human colorectal cancer cell lines tested (LoVo and Colo205 cells). There was also synergism between liposomal curcumin and oxaliplatin at a ratio of 4:1 in LoVo cells in vitro. In vivo, significant tumor growth inhibition was observed in Colo205 and LoVo xenografts, and the growth inhibition by liposomal curcumin was greater than that for oxaliplatin (P < 0.05) in Colo205 cells. Tumors from animals treated with liposomal curcumin showed an antiangiogenic effect, including attenuation of CD31 (an endothelial marker), vascular endothelial growth factor, and interleukin-8 expression by immunohistochemistry. This study establishes the comparable or greater growth-inhibitory and apoptotic effects of liposomal curcumin with oxaliplatin both in vitro and in vivo in colorectal cancer. We are currently developing liposomal curcumin for introduction into the clinical setting.
Curcumin, a yellow polyphenol extracted from the rhizome of turmeric (Curcuma longa), has potent anti-cancer properties as demonstrated in a plethora of human cancer cell line and animal carcinogenesis models. Nevertheless, widespread clinical application of this relatively efficacious agent in cancer and other diseases has been limited due to poor aqueous solubility, and consequently, minimal systemic bioavailability. Nanoparticle-based drug delivery approaches have the potential for rendering hydrophobic agents like curcumin dispersible in aqueous media, thus circumventing the pitfalls of poor solubility.
We have synthesized polymeric nanoparticle encapsulated formulation of curcumin - nanocurcumin - utilizing the micellar aggregates of cross-linked and random copolymers of N-isopropylacrylamide (NIPAAM), with N-vinyl-2-pyrrolidone (VP) and poly(ethyleneglycol)monoacrylate (PEG-A). Physico-chemical characterization of the polymeric nanoparticles by dynamic laser light scattering and transmission electron microscopy confirms a narrow size distribution in the 50 nm range. Nanocurcumin, unlike free curcumin, is readily dispersed in aqueous media. Nanocurcumin demonstrates comparable in vitro therapeutic efficacy to free curcumin against a panel of human pancreatic cancer cell lines, as assessed by cell viability and clonogenicity assays in soft agar. Further, nanocurcumin's mechanisms of action on pancreatic cancer cells mirror that of free curcumin, including induction of cellular apoptosis, blockade of nuclear factor kappa B (NFkappaB) activation, and downregulation of steady state levels of multiple pro-inflammatory cytokines (IL-6, IL-8, and TNFalpha).
Nanocurcumin provides an opportunity to expand the clinical repertoire of this efficacious agent by enabling ready aqueous dispersion. Future studies utilizing nanocurcumin are warranted in pre-clinical in vivo models of cancer and other diseases that might benefit from the effects of curcumin.
We have studied the freezing of a binary mixture of colloidal poly(methyl methacrylate) spheres of size ratio 0.31 and composition AB4 (here A refers to the larger spheres). When suspended in a suitable liquid these particles interact via a steeply repulsive (approximately hard sphere) potential. The structure of the colloidal crystals formed in this binary system has been established from a combination of small-angle neutron and light scattering measurements. We find that there is an almost complete size separation on freezing. The crystalline phase contains almost exclusively large spheres while the smaller spheres are excluded from the crystal into a coexisting binary fluid. This observation is in agreement with recent density functional calculations for the freezing of hard sphere mixtures.
The aim of the present study was to determine the kinetic equations for the thermal transformations of precipitated iron oxides
and hydroxides, namely for the process of thermal dehydroxylation of goethite and consecutive of hematite crystal structure
growth as well as for the oxidation of magnetite to maghemite and its thermal transformation into crystalline hematite. The
investigations have been carried out using thermogravimetry (TG/DTG/DTA), X-ray powder diffractometry (XRD) and high temperature
powder diffractometry (HT-XRD). This presentation contains the continuation of our earlier works.
The facile preparation of a mesoporous magnetic carrier technology is demonstrated. The micron-sized spherical mesostructured particles are prepared using a newly-developed, one-step, combined emulsion and solvent evaporation (ESE) method. The surfactant-templated silica matrix display a well-ordered internal pore architecture. Very limited pore blocking, and only to a limited degree disordered- or worm-like structures are observed, induced by the iron oxide nanoparticles added to provide the superparamagnetic properties.The iron oxide content was precisely controlled, and the magnetic properties were well preserved during the process. Finally we demonstrate the applicability of the magnetically separable mesoporous material as an adsorbent for specific dissolved materials from dilute aqueous solutions.
Using X-ray scattering over a large range of scattering vectors, it is shown how to measure both the pore volume fraction and pore specific surface of an assembly of porous grains forming a powder. Depending on the presence or not of solvent in the inner pores and in the intergranular media, the scattered signal per unit volume of solid or per unit volume of grain are introduced, which allow a complete analysis even when the thickness of the layer and its compactness are unknown. The method is applied to three different systems presenting a well defined Porod regime at large scattering vector.
The synthesis of inorganic materials with complex form, using surfactant assemblies as supramolecular templates1–13, has ramifications in areas as diverse as large-molecule catalysis, the formation of semiconductor nanostructures, biomolecule separations, the development of medical implants and the morphogenesis of skeletal forms14. Here we describe a procedure for the synthesis of hexagonal mesoporous silica that produces a remarkable array of shapes, surface patterns and channel plans. Our reaction conditions favour curved morphologies including toroidal, disk-like, spiral and spheroidal shapes. We use scanning electron microscopy to catalogue the basic topologies and surface patterns, and transmission electron microscopy to establish the relationship between morphology and the underlying mesostructure. Polarized optical microscopy enables us to identify a connection between optical anisotropy in these structures and the periodic porous mesostructure. We propose that the morphogenesis of these shapes and surface patterns can be rationalized in terms of the growth of a silicate liquid-crystal embryo15,16 with a hexagonal cross-section that, under different initial reaction conditions, is subject to increasing degrees of curvature.
Chemisorption of propionic acid vapors by an iron impregnated MCM-41 porous silica leads to the formation of iron−propionate species that upon pyrolysis can be transformed into γ-Fe2O3 nanoparticles of uniform size (150 Å) and homogeneously dispersed on the external surfaces of the porous silica support. The effect of the carboxylic acid nature on the size of the magnetic particles was examined. The magnetically modified MCM-41 solid retains its crystallinity and large surface area and can be functionalized with various organosilicon ligands, e.g., (CH3O)3SiCH2CH2CH2NHCH2CH2NH2, to produce novel reconstructed MCM-41 derivatives without destroying the magnetic properties of the parent material. The various steps in the synthesis and functionalization, as well as the nature, size, and location of the particles into the final solids were studied by means of IR and XRD, bulk magnetic measurements, Mössbauer, BET, and TEM techniques.
A water-in-oil microemulsion method has been applied for the preparation of silica-coated iron oxide nanoparticles. Three different nonionic surfactants (Triton X-100, Igepal CO-520, and Brij-97) have been used for the preparation of microemulsions, and their effects on the particle size, crystallinity, and the magnetic properties have been studied. The iron oxide nanoparticles are formed by the coprecipitation reaction of ferrous and ferric salts with inorganic bases. A strong base, NaOH, and a comparatively mild base, NH4OH, have been used in each surfactant to observe whether the basicity has some influence on the crystallization process during particle formation. Transmission electron microscopy, X-ray electron diffraction, and superconducting quantum interference device magnetometry have been employed to study both uncoated and silica-coated iron oxide nanoparticles. All these particles show magnetic behavior close to that of superparamagnetic materials. By use of this method, magnetic nanoparticles as small as 1−2 nm and of very uniform size (percentage standard deviation is less than 10%) have been synthesized. A uniform silica coating as thin as 1 nm encapsulating the bare nanoparticles is formed by the base-catalyzed hydrolysis and the polymerization reaction of tetraethyl orthosilicate in microemulsion. All experimental results are also compared with those for particles synthesized in pure water.
Mesoporöse Materialien auf Silicat-Basis wurden erstmals in den frühen neunziger Jahren bei Mobil untersucht. Diese Verbindungen wiesen Porengrößen zwischen 20 und 500 Å sowie spezifische Oberflächen von bis zu 1500 m2 g−1 auf und wurden nach einem neuartigen Flüssigkristalltemplatansatz hergestellt. Die Methode wurde auf die Synthese mesoporöser Übergangsmetalloxide ausgedehnt, die wegen ihrer variablen Oxidationsstufen und besetzten d-Bänder – Eigenschaften, die Silicate nicht aufweisen – als Katalysatoren sowie zur Herstellung elektronischer und magnetischer Bauelemente nützlich sind. Schon jetzt werden diese Materialien auf viel versprechende Weise in der Elektronik und Optik eingesetzt, was an den Halbleitereigenschaften von Übergangsmetalloxiden und an ihren Elektronenacceptorfähigkeiten liegt – einer wichtigen Eigenschaft im Hinblick auf das Design neuartiger Kathodenmaterialien. Dies ist die erste umfassende Übersicht über nichtsilicatische mesoporöse Materialien, in der die neueren Entwicklungen auf diesem Gebiet im Vordergrund stehen. Besonders ausführlich werden Materialien behandelt, die einzigartige elektronische, magnetische oder optische Eigenschaften aufweisen. Auch werden die Fortschritte bei Synthesen und Anwendungen mesostrukturierter Sulfide und neuartiger, über Templatsynthesen hergestellter Platin-haltiger Materialien beschrieben, die für Anwendungen in der heterogenen Katalyse viel versprechend erscheinen.
Continuous flow spinning disc processing (SDP), which has extremely rapid mixing under plug flow conditions, effective heat and mass transfer, allowing high throughput with low wastage solvent efficiency, is effective in gaining access to superparamagnetic Fe3O4 nanoparticles at room temperature. These are formed by passing ammonia gas over a thin aqueous film of Fe2+/3+ which is introduced through a jet feed close to the centre of a rapidly rotating disc (500 to 2500 rpm), the particle size being controlled with a narrow size distribution over the range 5 nm to 10 nm, and the material having very high saturation magnetizations, in the range 68–78 emu g−1.
Some pharmacological actions of curcumin (diferuloyl methane) have been examined in rats, mice and cats. The compound possesses significant anti-inflammatory activity in acute as well as in chronic models of inflammation. It is as potent as phenylbutazone in the carrageenan oedema test but only half as potent in chronic tests. Curcumin possesses a much lower ulcerogenic index than phenylbutazone. It prevents the inflammation induced increase in SGOT and SGPT levels. It lacks analgesic and antipyretic activity. It has no other significant pharmacological effects. The oral LD50 in mice is more than 2ṁ0 g kg−1.
We examined the inhibitory effects of curcumin and tetrahydrocurcumin (THC), one of the major metabolites of curcumin, on the lipid peroxidation of erythrocyte membrane ghosts induced by tertbutylhydroperoxide. The results demonstrated that THC showed a greater inhibitory effect than curcumin. To investigate the mechanism of antioxidative activity, we examined the effects of several inhibitors, such as antioxidant enzymes, hydroxyl radical scavengers, 1O2 quencher, and chelating agents for metal ions. Given that all inhibitors failed to inhibit membrane peroxidation, THC must scavenge radicals such as tert-butoxyl radical and peroxyl radical. To clarify the antioxidative mechanism of THC, in particular the role of the beta-diketone moiety, dimethylated THC was incubated with peroxyl radicals generated by thermolysis of 2,2'-azobis(2,4-dimethylvaleronitrile). Four oxidation products were detected, three of which were identified as 3,4-dimethoxybenzoic acid, 3',4'-dimethoxyacetophenone, and 3-(3,4-dimethoxyphenyl)-propionic acid. The fourth oxidation product seems to be an unstable intermediate, and its detailed structure has not been determined. These results suggest that the beta-diketone moiety of THC must exhibit antioxidative activity by cleavage of the C-C bond at the active methylene carbon between two carbonyls in the beta-diketone moiety. Because THC is one of the major metabolites of curcumin, it may also exhibit the same physiological and pharmacological properties as the active form of curcumin in vivo by means of the beta-diketone moiety as well as phenolic hydroxy groups.
The medicinal properties of curcumin obtained from Curcuma longa L. cannot be utilised because of poor bioavailability due to its rapid metabolism in the liver and intestinal wall. In this study, the effect of combining piperine, a known inhibitor of hepatic and intestinal glucuronidation, was evaluated on the bioavailability of curcumin in rats and healthy human volunteers. When curcumin was given alone, in the dose 2 g/kg to rats, moderate serum concentrations were achieved over a period of 4 h. Concomitant administration of piperine 20 mg/kg increased the serum concentration of curcumin for a short period of 1-2 h post drug. Time to maximum was significantly increased (P < 0.02) while elimination half life and clearance significantly decreased (P < 0.02), and the bioavailability was increased by 154%. On the other hand in humans after a dose of 2 g curcumin alone, serum levels were either undetectable or very low. Concomitant administration of piperine 20 mg produced much higher concentrations from 0.25 to 1 h post drug (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h), the increase in bioavailability was 2000%. The study shows that in the dosages used, piperine enhances the serum concentration, extent of absorption and bioavailability of curcumin in both rats and humans with no adverse effects.
Tissue repair and wound healing are complex processes that involve inflammation, granulation, and remodeling of the tissue. In this study, we evaluated the in vivo effects of curcumin (difeurloylmethane), a natural product obtained from the rhizomes of Curcuma longa on wound healing in rats and guinea pigs. We observed faster wound closure of punch wounds in curcumin-treated animals in comparison with untreated controls. Biopsies of the wound showed reepithelialization of the epidermis and increased migration of various cells including myofibroblasts, fibroblasts, and macrophages in the wound bed. Multiple areas within the dermis showed extensive neovascularization, and Masson's Trichrome staining showed greater collagen deposition in curcumin-treated wounds. Immunohistochemical localization of transforming growth factor-beta1 showed an increase in curcumin-treated wounds as compared with untreated wounds. In situ hybridization and polymerase chain reaction analysis also showed an increase in the mRNA transcripts of transforming growth factor-beta1 and fibronectin in curcumin-treated wounds. Because transforming growth factor-beta1 is known to enhance wound healing, it may be possible that transforming growth factor-beta1 plays an important role in the enhancement of wound healing by curcumin.
Liposomes have been proposed as carriers for the delivery of therapeutic and diagnostic agents to the lymphatic system. Subcutaneous (s.c.) injection is the route of administration most extensively studied for this purpose. Decisive factors influencing lymphatic absorption and lymph node uptake of s.c. administered liposomes are liposome size and the anatomical site of injection. Generally, other factors such as lipid composition, charge and the presence of a hydrophilic PEG-coating on the liposome surface do not substantially affect lymphatic absorption and lymph node uptake of s.c. administered liposomes. Studies on the intranodal fate of liposomes demonstrate that phagocytosis by macrophages is the most important mechanism for lymph node uptake of liposomes. The observation of relatively high uptake of liposomes in regional lymph nodes after s.c. administration has stimulated research on lymphatic targeting of liposomes for diagnostic and therapeutic applications.
Work in mesoporous silica-based materials began in the early 1990s with work by Mobil. These materials had pore sizes from 20-500 A and surface areas of up to 1500 m(2) g(-1) and were synthesized by a novel liquid crystal templating approach. Researchers subsequently extended this strategy to the synthesis of mesoporous transition metal oxides, a class of materials useful in catalysis, electronic, and magnetic applications because of variable oxidation states, and populated d-bands-features not found in silicates. These materials are already showing promise in electronic and optical applications hinging on the semiconducting properties of transition metal oxides and their potential to act as electron acceptors, an important feature in the design of cathodic materials. This is the first general review of non-silicate mesoporous materials and will focus on recent advances in this area, emphasizing materials possessing unique electronic, magnetic, or optical properties. Also covered are advances in the synthesis and applications of mesostructured sulfides as well as a new class of template-synthesized platinum-based materials that show promise in heterogeneous catalysis.
Fungicidal activity of Curcuma longa rhizome-derived materials against Botrytis cineria, Erysiphe graminis, Phytophthora infestans, Puccinia recondita, Pyricularia oryzae, and Rhizoctonia solani was tested using a whole plant method in vivo. It was compared with synthetic fungicides and four commercially available compounds derived from C. longa. The response varied with the tested plant pathogen. At 1000 mg/L, the hexane extract of C. longa showed fungicidal activities against E.graminis, P. infestans, and R. solani, and the ethyl acetate extract of C. longa showed fungicidal activities against B. cineria, P. infestans, Pu. recondita, and R. solani. Curcumin was isolated from the ethyl acetate fraction using chromatographic techniques and showed fungicidal activities against P. infestans, Pu. recondita, and R. solani with 100, 100, and 63% control values at 500 mg/L and 85, 76, and 45% control values at 250 mg/L, respectively. In the test with components derived from C. longa, turmerone exhibited weak activity against E. graminis, but no activity was observed from treatments with borneol, 1,8-cineole, sabinene, and turmerone. In comparison, potent fungicidal activity with chlorothalonil against P. infestans at 50 mg/L and dichlofluanid against B. cinerea at 50 mg/L was exhibited. These results may be an indication of at least one of the fungicidal actions of curcumin derived from C. longa.
An iron constitution: Dark superparamagnetic iron oxide nanoparticles are present within the walls of a hexagonal mesoporous aluminosilicate (as shown by the associated bright-field TEM image). The simple block-copolymer-based "one-pot" self-assembly approach enables potential applications in magnetic separation and catalyst technologies.
Research on wound healing drugs is a developing area in modern biomedical sciences. Scientists who are trying to develop newer drugs from natural resources are looking toward the Ayurveda, the Indian traditional system of medicine. Several drugs of plant, mineral, and animal origin are described in the Ayurveda for their wound healing properties under the term Vranaropaka. Most of these drugs are derived from plant origin. Some of these plants have been screened scientifically for the evaluation of their wound healing activity in different pharmacological models and patients, but the potential of most remains unexplored. In a few cases, active chemical constituents were identified. Some Ayurvedic medicinal plants, namely, Ficus bengalensis, Cynodon dactylon, Symplocos racemosa, Rubia cordifolia, Pterocarpus santalinus, Ficus racemosa, Glycyrrhiza glabra, Berberis aristata, Curcuma longa, Centella asiatica, Euphorbia nerifolia, and Aloe vera, were found to be effective in experimental models. This paper presents a limited review of plants used in Ayurvedic medicine.
Chemoprevention is a promising anti-cancer approach with reduced secondary effects in comparison to classical chemotherapy. Curcumin, one of the most studied chemopreventive agents, is a natural compound extracted from Curcuma longa L. that allows suppression, retardation or inversion of carcinogenesis. Curcumin is also described as an anti-tumoral, anti-oxidant and anti-inflammatory agent capable of inducing apoptosis in numerous cellular systems. In this review, we describe both properties and mode of action of curcumin on carcinogenesis, gene expression mechanisms and drug metabolism.
Nuclear factor-kappaB (NF-kappaB) plays a central role in cell survival and proliferation in human melanoma; therefore, the authors explored the possibility of exploiting NF-kappaB for melanoma treatment by using curcumin, an agent with known, potent, NF-kappaB-inhibitory activity and little toxicity in humans.
Three melanoma cell lines (C32, G-361, and WM 266-4), all of which had B-raf mutations, were treated with curcumin, and the authors assessed its effects on viability ((3-[4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium bromide assay) and apoptosis (flow-cytometric analysis of annexin V/propidium iodide-stained cells). Curcumin-treated cells also were examined for NF-kappaB binding activity (electrophoretic mobility shift assay) and for the activity of its upstream regulator, IkappaB kinase (IKK) (immune complex kinase assay). In addition, relevant signaling, as reflected by B-Raf kinase activity (kinase cascade assay), and steady-state levels of activated, downstream effectors, as reflected by mitogen-activated signal-regulated protein kinase (MEK), extracellular signal-regulated protein kinase (ERK), and Akt phosphorylation levels (immunoblots), were assessed.
Curcumin treatment decreased cell viability of all 3 cell lines in a dose-dependent manner (50% inhibitory concentration = 6.1-7.7 microM) and induced apoptosis. NF-kappaB and IKK were active constitutively in all melanoma cell lines examined, and curcumin, under apoptosis-inducing conditions, down-regulated NF-kappaB and IKK activities. However, curcumin did not inhibit the activities of B-Raf, MEK, or ERK, and Akt phosphorylation was enhanced. Furthermore, in the presence of curcumin, the Akt inhibitor 1L-6-hydroxymethyl-chiro-inositol 2-[(R)-2-O-methyl-3-O-octadecylcarbonate] no longer suppressed Akt phosphorylation.
Curcumin has potent antiproliferative and proapoptotic effects in melanoma cells. These effects were associated with the suppression of NF-kappaB and IKK activities but were independent of the B-Raf/MEK/ERK and Akt pathways.
Bisphosphonates have been confined in siliceous ordered mesoporous materials, and the drug release rate of these systems has been investigated. The bisphosphonate adsorption rate has been increased from 1% in oral administration to around 40% locally delivered. Drug dosage can be modulated through amine modification of the material surface, leading to a bisphosphonate adsorption in the ordered mesoporous matrices 3 times larger than that for unmodified materials. The use of these drug delivery systems opens new fields with new possibilities for tissue engineering.
The simultaneous entrapment of biological macromolecules and nanostructured silica-coated magnetite in sol-gel materials using a reverse-micelle technique leads to a bioactive, mechanically stable, nanometer-sized, and magnetically separable particles. These spherical particles have a typical diameter of 53 +/- 4 nm, a large surface area of 330 m(2)/g, an average pore diameter of 1.5 nm, a total pore volume of 1.427 cm(3)/g and a saturated magnetization (M(S)) of 3.2 emu/g. Peroxidase entrapped in these particles shows Michaelis-Mentan kinetics and high activity. The catalytic reaction will take place immediately after adding these particles to the reaction solution. These enzyme entrapping particles catalysts can be easily separated from the reaction mixture by simply using an external magnetic field. Experiments have proved that these catalysts have a long-term stability toward temperature and pH change, as compared to free enzyme molecules. To further prove the application of this novel magnetic biomaterial in analytical chemistry, a magnetic-separation immunoassay system was also developed for the quantitative determination of gentamicin. The calibration for gentamicin has a working range of 200-4000 ng/mL, with a detection limit of 160 ng/mL, which is close to that of the fluorescent polarization immunoassay (FPIA) using the same reactants.
The self-assembly of ultrabright fluorescent silica particles, which are applied in tagging, tracing, and labeling was investigated. The self-assembly is a novel synthesis of mesoporous silica particles with encapsulated organic dyes, in which the dyes are physically entrapped inside a silica matrix. Fluorescence was generated by the incorporation of inorganic or organic fluorescent dyes into the particle's material. Incorporation of dyes into a silica matrix is a difficult process because of the excellent sealing ability of silica and compatibility of silica with other materials. High concentration of the fluorescent dyes reached inside the pores without dimerization of the fluorescent molecules. The process of self-organization of mesoporous silica through acidic cationic surfactant templating and condensation of silica precursors was used to synthesize the mesoporous silica particles. Results show that the particles have the brightest fluorescent particles synthesized so far.
Magnetite (Fe304) nanoparticles stabilised by sulfonatocalixarene macrocycles are readily accessible by a rapid in situ co-precipitation, and exhibit ferro-fluidic and superparamagnetic behaviour.
A site-selective controlled delivery system for controlled drug release is fabricated through the in situ assembly of stimuli-responsive ordered SBA-15 and magnetic particles. This approach is based on the formation of ordered mesoporous silica with magnetic particles formed from Fe(CO)5 via the surfactant-template sol-gel method and control of transport through polymerization of N-isopropyl acrylamide inside the pores. Hydrophobic Fe(CO)5 acts as a swelling agent as well as being the source of the magnetic particles. The obtained system demonstrates a high pore diameter (7.1 nm) and pore volume (0.41 cm(3) g(-1)), which improves drug storage for relatively large molecules. Controlled drug release through the porous network is demonstrated by measuring the uptake and release of ibuprofen (IBU). The delivery system displays a high IBU storage capacity of 71.5 wt %, which is almost twice as large as the highest value based on SBA-15 ever reported. In vitro testing of IBU loading and release exhibits a pronounced transition at around 32 degrees C, indicating a typical thermosensitive controlled release.
Curcumin is recognized as a potential chemotherapeutic agent against a variety of tumors. However, the clinical application of curcumin is hindered due to its poor water solubility and fast degradation. The objective of this study was to investigate amphiphilic block copolymer micelles of poly(ethylene oxide)-b-poly(epsilon-caprolactone) (PEO-PCL) as vehicles for the solubilization, stabilization, and controlled delivery of curcumin. Curcumin-loaded PEO-PCL micelles were prepared by a cosolvent evaporation technique. PEO-PCL micelles were able to solubilize curcumin effectively, protect the encapsulated curcumin from hydrolytical degradation in physiological matrix, and control the release of curcumin over a few days. The characteristics of resultant micelles were found to depend on the polymerization degrees of epsilon-caprolactone. Among different PEO-PCL micelles, PEO(5000)-PCL(24500) was the most efficient in solubilizing curcumin while PEO(5000)-PCL(13000) was the best carrier in reducing its release rate. PEO-PCL micelle-encapsulated curcumin retained its cytotoxicity in B16-F10, a mouse melanoma cell line, and SP-53, Mino, and JeKo-1 human mantle cell lymphoma cell lines. These results demonstrated the potential of PEO-PCL micelles as an injectable formulation for efficient solubilization, stabilization, and controlled delivery of curcumin.
- T K Biswas
- B Mukherjee
T. K. Biswas, B. Mukherjee, Int. J. Low Extrem. Wounds 2003, 2, 25.
- O Spalla
- S Lyonnard
- F Testard
O. Spalla, S. Lyonnard, F. Testard, J. Appl. Crystallogr. 2003, 36, 338.
Received: December 30, 2008
- X He
- D Antonelli
- Angew B Bourlinos
- A Simopoulos
- N Boukos
- D Petridis
X. He, D. Antonelli, Angew. Chem. 2002, 114, 222; Angew. Chem.
Int. Ed. 2002, 41, 214.
[14] a) A. B. Bourlinos, A. Simopoulos, N. Boukos, D. Petridis, J. Phys.
Chem. B 2001, 105, 7432; b) S. Zhu, Z. Zhou, D. Zhang, ChemPhys-
Chem 2007, 8, 2478.
Iron Oxides in the Laboratory: Preparation and Characterization
- U Schwertmann
- R M Cornell
U. Schwertmann, R. M. Cornell, Iron Oxides in the Laboratory:
Preparation and Characterization, VCH, Weinheim, 1991.
- P Bartlett
- R H Ottewill
- S F Chin
- K S Iyer
- C L Raston
- M Saunders
P. Bartlett, R. H. Ottewill, J. Chem. Phys. 1992, 96, 3306.
[23] a) S. F. Chin, K. S. Iyer, C. L. Raston, M. Saunders, Adv. Funct.
Mater. 2008, 18, 922; b) S. F. Chin, M. Makha, C. L. Raston, M. Saunders, Chem. Commun. 2007, 1948.
- S Santra
- R Tapec
- N Theodoropoulou
- J Dobso
- A Hebard
- W Tan
S. Santra, R. Tapec, N. Theodoropoulou, J. Dobso, A. Hebard, W.
Tan, Langmuir 2001, 17, 2900.
- M K Kim
- G J Choi
- H S Lee
M. K. Kim, G. J. Choi, H. S. Lee, J. Agric. Food Chem. 2003, 51,
1578.
- Y Sugiyama
- S Kawakishi
- T Osawa
Y. Sugiyama, S. Kawakishi, T. Osawa, Biochem. Pharmacol. 1996,
52, 519.
- A Duvoix
- R Blasius
- S Delhalle
- M Schnekenburger
- F Morceau
- E Henry
- M Dicato
- M Diederich
- Cancer Lett
- D R Siwak
- S Shishodia
A. Duvoix, R. Blasius, S. Delhalle, M. Schnekenburger, F. Morceau, E. Henry, M. Dicato, M. Diederich, Cancer Lett. 2005, 223,
181; b) B. B. Aggarwal, A. Kumar, A. C. Bharti, Anticancer Res.
2003, 23, 363; c) D. R. Siwak, S. Shishodia, B. B. Aggarwal, R. Kurzrock, Cancer Lett. 2005, 104, 879.
- T N Shankar
- N V Shantha
- H P Ramesh
- I A Murthy
- V S Murthy
T. N. Shankar, N. V. Shantha, H. P. Ramesh, I. A. Murthy, V. S.
Murthy, India J. Exp. Biol 1980, 18, 73.
- X He
- D Antonelli
X. He, D. Antonelli, Angew. Chem. 2002, 114, 222; Angew. Chem.
Int. Ed. 2002, 41, 214.
- Yang
- Garcia