ArticleLiterature Review

Pharmaceutical liposomal drug delivery: a review of new delivery systems and a look at the regulatory landscape

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Abstract

Liposomes were the first nanoscale drug to be approved for clinical use in 1995. Since then, the technology has grown considerably, and pioneering recent work in liposome-based delivery systems has brought about remarkable developments with significant clinical implications. This includes long-circulating liposomes, stimuli-responsive liposomes, nebulized liposomes, elastic liposomes for topical, oral and transdermal delivery and covalent lipid-drug complexes for improved drug plasma membrane crossing and targeting to specific organelles. While the regulatory bodies’ opinion on liposomes is well-documented, current guidance that address new delivery systems are not. This review describes, in depth, the current state-of-the-art of these new liposomal delivery systems and provides a critical overview of the current regulatory landscape surrounding commercialization efforts of higher-level complexity systems, the expected requirements and the hurdles faced by companies seeking to bring novel liposome-based systems for clinical use to market.

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... The integration of materials that impart elasticity on the outer surface also contributes to the high elasticity of transfersomes. The high degree of elasticity of the vesicles enhances the delivery of herbal remedies across the skin and accelerates the rate of absorption during the healing process [192]. ...
... Ethanol in ethosomes increases membrane fluidity and permeability by interacting with the lipid molecules of the hydrophilic head regions of the bilayer. This synergy permits the efficient transdermal delivery of herbal medicines for medicinal purposes [192]. For instance, curcumin in ethosomal formulation might be used as a cutaneous delivery for improved wound healing and antimicrobial activity. ...
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The treatment of wounds is a serious problem all over the world and imposes a huge financial burden on each and every nation. For a long time, researchers have explored wound dressing that speeds up wound healing. Traditional wound dressing does not respond effectively to the wound-healing process as expected. Therapeutic active derived from plant extracts and extracted bioactive components have been employed in various regions of the globe since ancient times for the purpose of illness, prevention, and therapy. About 200 years ago, most medical treatments were based on herbal remedies. Especially in the West, the usage of herbal treatments began to wane in the 1960s as a result of the rise of allopathic medicine. In recent years, however, there has been a resurgence of interest in and demand for herbal medicines for a number of reasons, including claims about their efficacy, shifting consumer preferences toward natural medicines, high costs and negative side effects of modern medicines, and advancements in herbal medicines brought about by scientific research and technological innovation. The exploration of medicinal plants and their typical uses could potentially result in advanced pharmaceuticals that exhibit reduced adverse effects. This review aims to present an overview of the utilization of nanocarriers in plant-based therapeutics, including its current status, recent advancements, challenges, and future prospects. The objective is to equip researchers with a comprehensive understanding of the historical background, current state, and potential future developments in this emerging field. In light of this, the advantages of nanocarriers based delivery of natural wound healing treatments have been discussed, with a focus on nanofibers, nanoparticles, nano-emulsion, and nanogels.
... Liposomes with a higher EE% are capable of retaining elevated levels of the beneficial medicinal ingredient, leading to a reduction in production expenses. This improves pharmacokinetics and patient compliance [75]. ...
... The process of identifying CQAs and CPPs involves utilizing an experimental design that can effectively evaluate their impact on the CQAs [62]. The purpose of DS is to guarantee a superior product by exhibiting various formulation and/or process parameters [62,75]. DS includes product and process components. ...
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Nanomedicine is a developing discipline that is constantly evolving and differentiating. Liposomal preparation has an important role in nanomedicine as a novel platform. QbD involves drug formulation and advancement of a pharmaceutical medicament, including understanding of product quality and formulation steps, processing, and implementing controls to establish the product quality maintained by QbD. Primarily, drug and medicament governing bodies, including the USA and FDA, enhance product quality. Liposomal formulations and optimisation involve dependent and independent variables, requiring experience in optimisation. QbD is a risk-based approach used early in the pharmaceutical process to improve product quality and efficacy. Please shorten the given text so that it is more concise. QbD speeds up product development and ensures consistent, safe drug formulation in complex systems. In QbD, steps flow as adding variables related to CMAs, CPPs, and design places responsible for quality attributes for the final liposomal product preparation. QbD has recently been proposed as a tool for obtaining higher-quality liposomal nanocarriers. The broader structure of this research discusses the involvement of QbD as recent approach including their different parameters. Overall, lastly, the current practices that employ QbD in the optimisation and formulation of doxorubicin (DOX), by the using thin film-hydration extrusion technique primarily. DOX is antitumor class drug with a brand (Doxil®) loaded liposomal with TNF receptor as nanocarrier optimisation and formulation.
... Liposomes, consisting of a lipid layer and a core for encapsulating drugs, are among the first nano-scale materials for drug delivery. By modifying the lipid layer, liposomes can fulfill multiple functions, enabling effective drug delivery [9]. Polymer-based nanoparticles offer specific structures tailored for various applications, including gene/drug delivery [10,11]. ...
Article
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A diverse array of organic and inorganic materials, including nanomaterials, has been extensively employed in multifunctional biomedical applications. These applications encompass drug/gene delivery, tissue engineering, biosensors, photodynamic and photothermal therapy, and combinatorial sciences. Surface and bulk engineering of these materials, by incorporating biomolecules and aptamers, offers several advantages such as decreased cytotoxicity, improved stability, enhanced selectivity/sensitivity toward specific targets, and expanded multifunctional capabilities. In this comprehensive review, we specifically focus on aptamer-modified engineered materials for diverse biomedical applications. We delve into their mechanisms, advantages, and challenges, and provide an in-depth analysis of relevant literature references. This critical evaluation aims to enhance the scientific community's understanding of this field and inspire new ideas for future research endeavors.
... Changes in the structure of lipid bilayer lead to improved stability or skin permeability compared to traditional liposomes [68]. They enhance solubility, protect encapsulated molecules, and provide the controlled release of drugs [69]. For this reason, liposomes have become extremely popular as drug delivery systems for bioactive compounds. ...
Article
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As secondary plant metabolites, polyphenols are abundant in fruits and vegetables. They are in high demand because of their many health benefits. However, their low bioavailability makes them complex compounds to use for therapeutic purposes. Due to the limited solubility of phytocompounds, dietary supplements made from them may only be partially effective. Such molecules include fisetin, found in strawberries, and have shown great promise in treating Alzheimer’s disease and cancer. Unfortunately, because of their limited water solubility, low absorption, and poor bioavailability, the assistance of nanotechnology is required to allow them to fulfil their potential fully. Here, we provide evidence that nanodelivery methods and structure modifications can improve fisetin bioavailability, which is linked to improvements in therapeutic efficacy. An open question remains as to which nanocarrier should be chosen to meet the abovementioned requirements and be able to enhance fisetin’s therapeutic potential to treat a particular disease.
... Another strategy involves using a novel delivery system comprised of the M13 phage displaying a target-specific peptide or antibody conjugated to another vehicle (such as a liposome or an inorganic nanoparticle) (Fig. 5c). Liposomes are the most common and interesting lipid-based nanoparticles that have been approved by the FDA for drug delivery (Zylberberg and Matosevic, 2016;Dizaj et al., 2014). They have great characteristics such as good biocompatibility, easy biodegradation, little or no side effects, and a large loading capacity. ...
... Various nanocarriers including carbon nanotubes [15], liposomes [16], dendrimers [17], solid lipid nanoparticles (SLNs) [18], archaeosome [19], ethosomes, transferosomes [20], polymeric NPs [21], nanoemulsions [22], niosomes [23], and nanogels [24] were developed for drug delivery in recent decades. ...
Article
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This review highlights the potential benefits and drawbacks of using nanocarriers as drug delivery systems. Nanocarriers have been widely utilized to enhance drug efficiency, overcome drug resistance, and reduce adverse effects. However, the interaction between nanocarriers and biological systems can lead to toxic responses. Therefore, it is crucial to carefully select optimized nanocarriers to minimize toxicity and maximize efficiency. Every type of nanocarrier has its own advantages and disadvantages. Hybrid nanocarriers have been engineered to address the limitations of existing nanocarriers and are considered more suitable for developing new formulations. The article discusses various aspects of nanocarriers, including their applicability, potential toxicity, and strategies for utilizing appropriate nanocarriers in nanoformulations. To mitigate the toxicity of nanocarriers, several approaches can be employed, such as PEGylation, coating, charge coating, and injections of free PEG; moreover, by modifying the preparation method or utilizing hybrid nanocarriers, the efficiency of drug delivery systems can be improved. Overall, the article emphasizes the importance of selecting appropriate nanocarriers and employing strategies to reduce toxicity while enhancing drug delivery efficiency.
... Since then, the liposome technology has provided intelligent solutions to solve challenges in pharmacology, such as increasing drug solubility, reducing drug toxicity, and improving targeted drug release [1,2]. Liposomes have three distinct compartments that can be used to carry various compounds such as, e.g., drugs: the interior aqueous compartment; the hydrophobic bilayer; and the polar inter-phase of the inner and outer leaflet [3][4][5]. ...
Article
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This study aims to highlight the impact of physicochemical properties on the behaviour of nanopharmaceuticals and how much carrier structure and physiochemical characteristics weigh on the effects of a formulation. For this purpose, two commercially available nanosimilar formulations of Doxil and their respective carriers were compared as a case study. Although the two formulations were “similar”, we detected different toxicological effects (profiles) in terms of in vitro toxicity and immunological responses at the level of cytokines release and complement activation (iC3b fragment), that could be correlated with the differences in the physicochemical properties of the formulations. Shedding light on nanosimilar key quality attributes of liposome-based materials and the need for an accurate characterization, including investigation of the immunological effects, is of fundamental importance considering their great potential as delivery system for drugs, genes, or vaccines and the growing market demand.
... They represent a peculiar class of nanomedicines in which a limited number of drug molecules are conjugated per antibody unit and whose approval is based on the biological license applications (BLA) process. [3] Liposomes have been the first nanomedicine approved for clinical use and are still considered a useful and versatile approach that can be tailored to specific needs by tuning their size, morphology, composition, surface modification, etc. [4,5] To obtain a selective delivery to solid cancers, the approved liposomes loaded with cytotoxic drugs can rely only on passive tumor accumulation by exploiting the enhanced vascular permeability and retention (EPR) effect, due to their size. [6] However, the real benefits of EPR effects for significant tumor selectivity are still under debate [7][8][9] and some evidence suggest that only a minor fraction of the injected dose of a nanomedicine can reach the cancer site by exploiting the EPR effect. ...
Article
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Liposomes play an important role in the field of drug delivery by virtue of their biocompatibility and versatility as carriers. Stealth liposomes, obtained by surface decoration with hydrophilic polyethylene glycol (PEG) molecules, represented an important turning point in liposome technology, leading to significant improvements in the pharmacokinetic profile compared to naked liposomes. Nevertheless, the generation of effective targeted liposomes – a central issue for cancer therapy – has faced several difficulties and clinical phase failures. Active targeting remains a challenge for liposomes. In this direction, we designed a new Super Stealth Immunoliposomes (SSIL2) composed of a PEG‐bi‐phospholipids derivative that stabilizes the polymer shielding over the liposomes. Furthermore, its counterpart, conjugated to the fragment antigen‐binding of trastuzumab (Fab’ TRZ ‐PEG‐bi‐phospholipids), is firmly anchored on the liposomes surface and correctly orients outward the targeting moiety. Throughout this study, the performances of SSIL2 are evaluated and compared to classic stealth liposomes and stealth immunoliposomes in vitro in a panel of cell lines and in vivo studies in zebrafish larvae and rodent models. Overall, SSIL2 shows superior in vitro and in vivo outcomes, both in terms of safety and anticancer efficacy, thus representing a step forward in targeted cancer therapy, and valuable for future development. This article is protected by copyright. All rights reserved
... Organic NPs are biodegradable, non-toxic, and sensitive to heat and light. Examples include polymers [100][101][102][103], liposomes [104,105], micelles [106]. and dendrimers [107,108]. ...
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An emerging multidrug-resistant pathogenic yeast called Candida auris has a high potential to spread quickly among hospitalized patients and immunodeficient patients causing nosocomial outbreaks. It has the potential to cause pandemic outbreaks in about 45 nations with high mortality rates. Additionally, the fungus has become resistant to decontamination techniques and can survive for weeks in a hospital environment. Nanoparticles might be a good substitute to treat illnesses brought on by this newly discovered pathogen. Nanoparticles have become a trend and hot topic in recent years to combat this fatal fungus. This review gives a general insight into the epidemiology of C. auris and infection. It discusses the current conventional therapy and mechanism of resistance development. Furthermore, it focuses on nanoparticles, their different types, and up-to-date trials to evaluate the promising efficacy of nanoparticles with respect to C. auris.
... In addition to the cyclodextrin solution formulation, two liposome formulation systems were also developed. Liposomes have demonstrated, both in research and clinical settings, to be a promising system for delivery of complex payloads via the parenteral route [26]. They are versatile carriers, wherein a lipophilic drug can be encapsulated in the lipid bilayer and a hydrophilic drug can be encapsulated in the aqueous core. ...
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Proteolysis-Targeting Chimeras (PROTACs) are a promising new technology in drug development. They have rapidly evolved in recent years, with several of them in clinical trials. While most of these advances have been associated with monovalent protein degraders, bivalent PROTACs have also entered clinical trials, although progression to market has been limited. One of the reasons is the complex physicochemical properties of the heterobifunctional PROTACs. A promising strategy to improve pharmacokinetics of highly lipophilic compounds, such as PROTACs, is encapsulation in liposome systems. Here we describe liposome systems for intravenous administration to enhance the PK properties of two bivalent PROTAC molecules, by reducing clearance and increasing systemic coverage. We developed and characterized a PROTAC-in-cyclodextrin liposome system where the drug was retained in the liposome core. In PK studies at 1 mg/kg for GNE-01 the PROTAC-in-cyclodextrin liposome, compared to the solution formulation, showed a 80- and a 380-fold enhancement in AUC for mouse and rat studies, respectively. We further investigated the same PROTAC-in-cyclodextrin liposome system with the second PROTAC (GNE-02), where we monitored both lipid and drug concentrations in vivo. Similarly, in a mouse PK study of GEN-02, the PROTAC-in-cyclodextrin liposome system exhibited enhancement in plasma concentration of a 23× increase over the conventional solution formulation. Importantly, the lipid CL correlated with the drug CL. Additionally, we investigated a conventional liposome approach for GNE-02, where the PROTAC resides in the lipid bilayer. Here, a 5× increase in AUC was observed, compared to the conventional solution formulation, and the drug CL was faster than the lipid CL. These results indicate that the different liposome systems can be tailored to translate across multiple PROTAC systems to modulate and improve plasma concentrations. Optimization of the liposomes could further improve tumor concentration and improve the overall therapeutic index (TI). This delivery technology may be well suited to bring novel protein targeted PROTACs into clinics.
... In hydrophobic drugs, it could also be placed between the lipid bilayer of the cell membrane in a phagosomal form (Kumar et al., 2020). LPs used in biology and medicine display a range of benefits comprising high drug/lipid proportion loading efficacy, simplicity of synthesis in a size-controlled way, great stability, manageable delivery kinetics, and biocompatibility (Zylberberg and Matosevic, 2016). Moreover, LPs can be extra equipped with functional moieties to increase their performances in terms of increased circulation half-life, targeted delivery, and intracellular permeation capability (Kim, 2016). ...
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Various nanoparticles are used in the discovery of new nanomedicine to overcome the shortages of conventional drugs. Therefore, this article presents a comprehensive and up-to-date review of the effects of nanoparticle-based drugs in the treatment of respiratory disorders, including both basic and clinical studies. Databases, including PubMed, Web of Knowledge, and Scopus, were searched until the end of August 2022 regarding the effect of nanoparticles on respiratory diseases. As a new tool, nanomedicine offered promising applications for the treatment of pulmonary diseases. The basic composition and intrinsic characteristics of nanomaterials showed their effectiveness in treating pulmonary diseases. The efficiency of different nanomedicines has been demonstrated in experimental animal models of asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis (PF), lung cancer, lung infection, and other lung disorders, confirming their function in the improvement of respiratory disorders. Various types of nanomaterials, such as carbon nanotubes, dendrimers, polymeric nanomaterials, liposomes, quantum dots, and metal and metal oxide nanoparticles, have demonstrated therapeutic effects on respiratory disorders, which may lead to new possible remedies for various respiratory illnesses that could increase drug efficacy and decrease side effects.
... Although therapies such as chemotherapy are developed to be commonly used against cancer, their lack of specificity in distinguishing between cancerous and healthy cells, as well as the challenge of multidrug resistance, pose significant obstacles. Moreover, these treatments often leave behind serious side effects, including hair loss and bone marrow suppression [17] . Hence, the discovery of more accurate and target-specific drugs to address tumor cells has recently garnered increased attention. ...
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As a pathologically heterogeneous disease, cancer is one of the leading causes of global morbidity. According to the World Health Organization, approximately one in six deaths are caused by cancer. Fortunately, many cancers can be cured if diagnosed at early stages and treated efficiently. Despite the benefits of conventional cancer treatments such as surgery, chemotherapy, hormone therapy, and radiation therapy, they have several drawbacks, including cytotoxicity, inaccurate targeting of tumor cells, and multi-drug resistance, which underscore the importance of developing novel and effective strategies to improve diagnosis, prognosis, therapy, and patient survival. Recently, the advancement of nanotechnology has opened new horizons for cancer treatment thanks to the discovery of nanoparticles (NPs) and the small-sized molecules that revolutionized the drug delivery methods in cancerous tissues. The specific characteristics of NPs, such as reduced toxicity, improved permeability, and accurate targeting of tumor cells, provide a great advantage in cancer treatment and help to overcome the limitations and challenges of conventional cancer treatment methods. Besides, the role of NPs in immunotherapy has created a novel concept for cancer treatment. This review gives a brief overview regarding the importance of NPs and their targeting mechanism, as well as the challenges and limitations associated with their use in cancer treatment.
... Liposomes are thought to be biocompatible as well as biodegradable and due to their structure, they can carry both hydrophilic water-soluble molecules in the aqueous core and hydrophobic compounds in the lipid membrane, as previously shown 9 . Thus, large unilamellar vesicles (LUVs), with sizes of approximately 100 nm in diameter, have been successfully as carriers for antitumor drugs in cancer chemotherapy [10][11][12] and for gene delivery purposes 9,13 . These systems are designed to increase drug bioavailability, control drug delivery, and maintain intact drug delivery to the site of action 8 . ...
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Drug delivery systems are frequently used for targeted transport of pharmaceuticals and their controlled release at a destined target site. One of the most commonly used drug carriers are liposomes. Additionally, such drug-liposome system is used as model system for studying interaction processes at cellular or even molecular level. The aim of our work was to improve the understanding of drug carrier uptake mechanisms by applying fluorescence lifetime imaging microscopy (FLIM) and fluorescence correlation spectroscopy (FCS), both combined with two-photon (2P) excitation. We prepared giant unilamellar vesicles (GUVs) representing a simplified model system for cell membrane, labelled with the amphiphilic fluorescent dye 3,3'-dioctadecyloxacarbocyanine (DiOC 18 (3)). Furthermore, large unilamellar vesicles (LUVs) were used as a drug carrier system, containing the spectrally different fluorescent sulforhodamine 101 (SRh101) as drug imitate. Herein, we present results of the varying interaction between GUVs and LUVs depending on the used charged lipids. The exchange kinetics and structural changes of the liposome carriers during the fusion process were investigated. We also observed that the internalisation efficiency was mainly influenced by the vesicle´s lipid composition. We ultimately demonstrated that 2P-FLIM and FCS provide a unique methodological approach to study liposome interactions and use them as a versatile model system.
... Formulation optimization can help to identify the optimal liposome size, composition, and surface properties that are required to achieve the desired pharmacokinetic and pharmacodynamic properties. [117] Limited approval and insurance coverage, as well as high production costs, can reduce accessibility and affordability for patients. These challenges can be overcome by developing efficient production methods and advocating for favorable reimbursement policies. ...
Article
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Cardiovascular disease is the leading cause of death worldwide. Blood‐contacting medical devices provide critical support for patients with severe respiratory and/or cardiac failure. High shear stress zones and non‐biocompatible circuit can increase the risk of thrombus formation in patients. These thrombi restrict blood flow through the circuits and travel to the lungs and brain, creating significant consequences. Antithrombotic drugs are used to lower this risk, but they also raise the incidence of bleeding problems. This article explores the delicate balance between thrombosis and bleeding in medical devices by examining platelet activation and thrombosis formation under shear stress. The feasibility of a shear‐responsive nanomedicine‐based drug delivery system has been explored as a potential approach for targeted administration of antithrombotic medications to lower systemic drug levels and reduce the bleeding risk. Furthermore, the lack of in vitro platforms to investigate the biological behavior of antithrombotic nanoparticles is impeding their clinical translation. As a result, microfluidic technology offers a platform for investigating nanoparticle behavior in vitro and linking it to their performance in vivo. Finally, the challenges and factors that affect the functionality, stability, and circulation time of liposomal drugs are investigated to improve their efficacy for targeted drug administration in medical devices.
... They are self-assembled nanoparticles composed of lipid bilayers. 35 Liposomes are spherical vesicles composed of an inner aqueous core and outer chemically active one to several concentric lipid bilayers. The lipid bilayersengage hydrophilic heads and hydrophobic hydrocarbon tails encapsulating the aqueous spaces. ...
Article
Nanotechnology is science, engineering and technology conducted at the nanoscale that deals with the development and application of nanoparticles or nanomaterials. This field is considered as the greatest of all inventions humans have ever made till date. The associated research and applications are diverse, ranging from extensions of conventional technology to new approaches based upon the property of molecular self-assembly. Nanotechnology has been greatly advanced in the past few decades and the role of nanotechnology in field of dentistry and particularly in periodontology has evolved greatly. The use of various nanoparticles and materials has brought a new insight into the prevention, diagnosis and management of periodontal disease. In the near futureinvention of dental nanorobots will help in precise diagnosis and may lead us to new treatment opportunities. This review focuses on the updated applications of nanotechnology in the field of Periodontics.
... Liposomes have been extensively used for the delivery of drugs. Many liposomebased drugs, including the chemotherapeutics doxorubicin, daunorubicin and vincristine, were approved by the FDA and are on the market [48]. As shown in Figure 6, liposomes containing C4a promoted a slow release of this ABCG2 inhibitor. ...
Article
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Inhibition of ABC transporters is a promising approach to overcome multidrug resistance in cancer. Herein, we report the characterization of a potent ABCG2 inhibitor, namely, chromone 4a (C4a). Molecular docking and in vitro assays using ABCG2 and P-glycoprotein (P-gp) expressing membrane vesicles of insect cells revealed that C4a interacts with both transporters, while showing selectivity toward ABCG2 using cell-based transport assays. C4a inhibited the ABCG2-mediated efflux of different substrates and molecular dynamic simulations demonstrated that C4a binds in the Ko143-binding pocket. Liposomes and extracellular vesicles (EVs) of Giardia intestinalis and human blood were used to successfully bypass the poor water solubility and delivery of C4a as assessed by inhibition of the ABCG2 function. Human blood EVs also promoted delivery of the well-known P-gp inhibitor, elacridar. Here, for the first time, we demonstrated the potential use of plasma circulating EVs for drug delivery of hydrophobic drugs targeting membrane proteins.
... Organic NPs have indeed been utilized for many years and come in a variety of subclasses. The liposomes are the first introduced nano-sized clinically approved drug carriers, including an inner core that can be used to encapsulate either hydrophilic or hydrophobic medicines and an outside lipid layer [58]. The lipid layer of liposomes can be functionalized to obtain many functions, e.g., modifying the biophysical features (mobility and deformation) of living cells, which is beneficial for effective therapeutic drug delivery. ...
Article
In recent years, the incidence and mortality rate of cancer is raising worldwide. Traditional approaches for cancer patient management including surgery, chemotherapy, radiotherapy, and targeted therapies provide unsatisfactory results and are often associated with adverse reactions. Over the last few decades, nanotechnology has been a rapidly emerging area of theragnostic in clinical research. It plays a vital role as a bridge between the science and technology of miscellaneous nanoparticles (NPs) and nanomedicine. In general, NPs with a range of sizes of 1–100 nm are thought to be acceptable for cancer medications. NPs may enhance the consistency and solubility of therapeutic drugs to obtain site-specific targeting, controlled release, and safe for healthy organs. NPs have the benefit of pathophysiological properties, enhanced permeability and retention (EPR) effects, and an advantage in cancer targeting. Furthermore, theranostic nanoparticles have been established having incorporated diagnostics and therapy in a single system that might provide more personalized treatment with optimal doses and monitoring the distribution, targeting, and response to therapy by using imaging tools. In this review, we have discussed the classes of nanoparticles, targeting approaches, and implications of NPs for cancer theranostics with recent examples.
... Liposomes are the first nanoscale drug that have been clinically approved for therapeutic applications. 182 These nanospheres comprise of naturally occurring or artificially ...
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Nanotechnology has gained immense appraisal owing to its multidimensional advantages in the scientific world. Recent progress has confirmed nanostructured architectures to possess promising medicinal applications which have triggered its investigation as Nano-drug delivery vehicles. These engineered vehicles offer an unprecedented platform for controlled release of encapsulated drug to targeted site with higher effectuality and reduced toxicity by overcoming the loopholes allied with the conventional drug delivery systems. This review provides a systematic overview of specific properties of nanostructured materials viz., inorganic nanoparticles, polymeric micelles, chitosan, liposomes, dendrimers, carbon nanotubes, quantum dots, niosomes etc. and consolidates their therapeutic approaches in the diagnosis and treatment of chronic diseases like Cancer, COVID-19, HIV/AIDS. Factors including interactions of nanomaterials with physiological environment, mode of drug administration, stability of the therapeutic agents and mechanism of action etc. have been summarized for attaining efficacious drug delivery. In addition to opportunities, the challenges of nanomedicines in drug delivery have also been insighted. In the futuristic perspective further advancement is necessitated in the domain of Nanotechnology mediated advanced drug delivery system by combining newer treatment approaches such as gene therapy, immunotherapy etc. with the existing nanotechnology to improve the performance of the drugs and maximize the efficiency of targeted drug distribution.
... Liposomes have been widely used as a carrier to deliver both hydrophilic and hydrophobic drugs, antibacterial and antifungal agents, vaccines, Enzs, and genetic cargo [99]. This popularity refers to high drug/lipid ratio loading efficiency, ease of fabrication in a size-controlled manner, long-circulating by polyethylene glycol (PEG) coating, excellent stability, controllable release kinetics, and biocompatibility [100]. Liposomal formulations have shown an ability to enhance the PK and PD of active pharmaceutical ingredients (API), while hindering their associated off-target toxicity [101]. ...
Article
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Enzyme (Enz)-mediated therapy indicated a remarkable effect in the treatment of many human cancers and diseases with an insight into clinical phases. Because of insufficient immobilization (Imb) approach and ineffective carrier, Enz therapeutic exhibits low biological efficacy and bio-physicochemical stability. Although efforts have been made to remove the limitations mentioned in clinical trials, efficient Imb-destabilization and modification of nanoparticles (NPs) remain challenging. NP internalization through insufficient membrane permeability, precise endosomal escape, and endonuclease protection following release are the primary development approaches. In recent years, innovative manipulation of the material for Enz immobilization (EI) fabrication and NP preparation has enabled nanomaterial platforms to improve Enz therapeutic outcomes and provide low-diverse clinical applications. In this review article, we examine recent advances in EI approaches and emerging views and explore the impact of Enz-mediated NPs on clinical therapeutic outcomes with at least diverse effects. Graphical abstract
... In 1995, liposomes became the first nanoscale medicine to receive FDA approval for clinical use. Since then, the technology has advanced significantly, and pioneering recent work in liposome-based delivery systems has resulted in major advances with important therapeutic applications [82]. Liposomes have been investigated extensively for many years as a drug carrier and have demonstrated to have promising potential for curcumin delivery to in-vivo [83][84][85][86]. ...
Article
Curcumin is a polyphenol molecule derived from Curcuma longa Linn's rhizomes. Curcumin appears to have been the target of substantial research, with cancer, viral, fungal infections, bacterial, arthritis, antioxidant, anti-inflammatory, allergies, Alzheimer's disease, and other chronic diseases and disorders all being explored. Curcumin has undesirable features such as inadequate intake and low aqueous solubility. To resolve these challenges, research has taken numerous attempts to improve its absorption, solubility, and bioavailability. Nanotechnology plays a critical role in the creation of nanostructured devices, nanomedicines, targeted therapy, and nanocarriers. Curcumin nano formulation has alleviated some of the major disadvantages of curcumin-based medication delivery. The emphasis of the study is on nano-based techniques to address therapeutic activity, efficacy, bioavailability, and solubility. Curcumin was localized to a certain cellular and molecular level by combining nano-curcumin with a specific molecule to enhance activity at the target site. A detailed description of solubility and bioavailability enhancement technique using protein carriers, solid dispersions, nanofiber, carbon dots, liposomes, and polymer carrier drug delivery systems is provided in this review.
... Both inorganic and organic nanoparticles have been proposed for cancer therapy [29]. Among organic nanoparticles, liposomes are the very first nanosystem approved for the treatment of cancer, and still are the best-investigated platform in clinical trials and academic research [30][31][32][33]. They offer numerous advantages over therapies with free drugs: increased solubility and bioavailability of the loaded drug, controlled/constant rate of drug released over the desired timescale, protection of the loaded drug, selectivity against cancer targets, thus increased efficacy, and reduced dose of the administered drug, thus lower systemic toxicity [34][35][36]. ...
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Liver cancer is one of the most common causes of cancer death worldwide. In recent years, substantial progress has been made in the development of systemic therapies, but there is still the need for new drugs and technologies that can increase the survival and quality of life of patients. The present investigation reports the development of a liposomal formulation of a carbamate molecule, reported as ANP0903, previously tested as an inhibitor of HIV-1 protease and now evaluated for its ability to induce cytotoxicity in hepatocellular carcinoma cell lines. PEGylated liposomes were prepared and characterized. Small, oligolamellar vesicles were produced, as demonstrated by light scattering results and TEM images. The physical stability of the vesicles in biological fluids was demonstrated in vitro, alongside the stability during storage. An enhanced cellular uptake was verified in HepG2 cells treated with liposomal ANP0903, resulting in a greater cytotoxicity. Several biological assays were performed to elucidate the molecular mechanisms explaining the proapoptotic effect of ANP0903. Our results allow us to hypothesize that the cytotoxic action in tumor cells is probably due to the inhibition of the proteasome, resulting in an increase in the amount of ubiquitinated proteins within the cells, which in turn triggers activation of autophagy and apoptosis processes, resulting in cell death. The proposed liposomal formulation represents a promising approach to deliver a novel antitumor agent to cancer cells and enhance its activity.
... They can also transport hydrophilic and hydrophobic compounds as well as larger molecules. The improved pharmacological activity and efficacy should also be attributed to skin adhesion and the proximity of the nanosystems to the target cells [277][278][279]. The application of lipid nanosystems for transdermal drug delivery is discussed herein. ...
Article
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Skin delivery is an exciting and challenging field. It is a promising approach for effective drug delivery due to its ease of administration, ease of handling, high flexibility, controlled release, prolonged therapeutic effect, adaptability, and many other advantages. The main associated challenge, however, is low skin permeability. The skin is a healthy barrier that serves as the body's primary defence mechanism against foreign particles. New advances in skin delivery (both topical and transdermal) depend on overcoming the challenges associated with drug molecule permeation and skin irritation. These limitations can be overcome by employing new approaches such as lipid nanosystems. Due to their advantages (such as easy scaling, low cost, and remarkable stability) these systems have attracted interest from the scientific community. However, for a successful formulation, several factors including particle size, surface charge, components, etc. have to be understood and controlled. This review provided a brief overview of the structure of the skin as well as the different pathways of nanoparticle penetration. In addition, the main factors influencing the penetration of nanoparticles have been highlighted. Applications of lipid nanosystems for dermal and transdermal delivery, as well as regulatory aspects, were critically discussed.
... Both organic and inorganic nanoparticles [6] have been studied to improve tolerability, pharmacologic specificity, biodegradability, and targeting for oral drugs [7,8]. Numerous nanocarriers including nanoparticles [9,10], liposomes [11,12], emulsions [13] etc., have been applied for oral drugs. Most nanocarriers showed advantages in protecting drugs from harsh conditions in the GIT, increasing the drugs can be metabolized by the gut microflora which effects the release characters of drugs. ...
Article
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The oral route is the most preferred route for systemic and local drug delivery. However, the oral drug delivery system faces the harsh physiological and physicochemical environment of the gastrointestinal tract, which limits the bioavailability and targeted design of oral drug delivery system. Innovative pharmaceutical approaches including nanoparticulate formulations, biomimetic drug formulations, and microfabricated devices have been explored to optimize drug targeting and bioavailability. In this review, the anatomical factors, biochemical factors, and physiology factors that influence delivering drug via oral route are discussed and recent advance in conventional and novel oral drug delivery approaches for improving drug bioavailability and targeting ability are highlighted. We also address the challenges and opportunities of oral drug delivery systems in future.
... Organic NPs have been extensively studied over the recent years and contain a variety of types. The first nano-scale medication licensed for medical use is called a liposome [100]. Liposomes are biocompatible, biodegradable, and nontoxic vesicles. ...
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... Because of enhanced penetration and endurance, organic nanocarriers, such as micelles and liposomes, can aggregate at the appropriate location [71]. Because they are simple compounds, liposome-mediated drug delivery and polymeric nanocarriers are first-generation nanocarriers [72]. ...
... Summary of the liposomal drugs approved by the FDA and/or EMA for cancer treatment[28][29][30][31][32][33][34][35][36][37][38][39][40]. ...
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... Besides, lipid penetration and permeation occur due to the fusion of the ethosomes with skin lipids, called the ethosome effect. Because of the two effects, ethosomes show improved skin penetration.46 ...
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Lipid vesicles or more precisely liposome, is a term that is derived from two Greek words, 'Lipos' means fat and 'Soma' which means body. These spherical, self-contained structures have an inner core that is enclosed by one or more concentric lipid bilayers. Their size generally ranges from 20 nm to few microns and the thickness of lipid bilayer usually lies in nanoscale range. Since their inception in 1960s as conventional vesicles, they have witnessed tremendous technolgical development that has led to formation of 'second generation liposomes which possess long circulating time in body. Liposomes exhibits superior properties like better solubility , enhanced bioavailability, lower dose size, biodegradable nature of lipid bilayer etc, over the conventional drug delivery systems. Different methods are being employed for liposomes preparation like ether injection, hydration method, sonication, microemulsification, reverse evaporation, freeze thawed technique etc. The method of preparation depends on various parameters like lipid bilayer composition, route of administration, disease in which liposomal formulation is required etc. Liposomes are generally characterized for shape, size, surface properties, lamellarity, phase behaviour and drug release profile etc. This article briefly summarises the classification, methods of preparation, characterization and application of liposomes.
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One of the major limitations for the treatment of many diseases is an inability of drugs to cross the cell membrane barrier. Different kinds of carriers are being investigated to improve drug bioavailability. Among them, lipid or polymer-based systems are of special interest due to their biocompatibility. In our study, we combined dendritic and liposomal carriers and analysed the biochemical and biophysical properties of these formulations. Two preparation methods of Liposomal Locked-in Dendrimers (LLDs) systems have been established and compared. Carbosilane ruthenium metallodendrimer was complexed with an anti-cancer drug (doxorubicin) and locked in a liposomal structure, using both techniques. The LLDs systems formed by hydrophilic locking had more efficient transfection profiles and interacted with the erythrocyte membrane better than systems using the hydrophobic method. The results indicate these systems have improved transfection properties when compared to non-complexed components. The coating of dendrimers with lipids significantly reduced their hemotoxicity and cytotoxicity. The nanometric size, low polydispersity index and reduced positive zeta potential of such complexes made them attractive for future application in drug delivery. The formulations prepared by the hydrophobic locking protocol were not effective and will not be considered furthermore as prospective drug delivery systems. In contrast, the formulations formed by the hydrophilic loading method have shown promising results where the cytotoxicity of LLD systems with doxorubicin was more effective against cancer than normal cells.
Chapter
Mitochondrial dysfunction in Parkinson’s Disease (PD) is implicated through both environmental exposure and genetic factors (Grünewald et al. 2016; Tzoulis et al. 2013; Flønes et al. 2018; Fonseca-Fonseca et al. 2021). The first evidence reported of mitochondrial dysfunction associated with PD was in 1983 when 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure caused parkinsonian-like symptoms (Langston et al. 1983; Langston and Ballard 1983). Currently, there are limited approved drugs for the treatment of PD and these drugs only offer treatment for symptomatic purposes (Zhen and Chu 2020). However, as research advancements emerge in this field, organ-specific targeted therapies are receiving high priority as future therapeutic approaches hence nano-drug carriers like liposomes came into the valuable options for the treatment of PD. Around 30 years ago, researchers found a new way of delivering medicinal substances to specific areas of the brain—by injecting them into a certain part, in this case, the rat’s striatum. Liposomes loaded with dopamine partially ameliorated the cognitive and motor deficits in a PD rat model, as well as demonstrated the importance of targeted delivery to the brain (During et al. 1992).
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Tamoxifen as an antiestrogen is successfully applied for the clinical treatment of breast cancer in pre- and post-menopausal women. Due to the side effects related to the oral administration of Tamoxifen (such as deep vein thrombosis, pulmonary embolism, hot flushes, ocular disturbances and some types of cancer), liposomal drug delivery is recommended for taking this drug. Drug encapsulation in a liposomal or lipid drug delivery system improves the pharmacokinetic and pharmacodynamic properties. In this regard, we carried out 200-ns molecular dynamics (MD) simulations for three systems (pure DPPC and neutral and protonated Tamoxifen-loaded DPPC). Here, DPPC is a model lipid bilayer to provide us with conditions like liposomal drug delivery systems to investigate the interactions between Tamoxifen and DPPC lipid bilayers and to estimate the preferred location and orientation of the drug molecule inside the bilayer membrane. Properties such as area per lipid, membrane thickness, lateral diffusion coefficient, order parameters and mass density, were surveyed. With insertion of neutral and protonated Tamoxifen inside the DPPC lipid bilayers, area per lipid and membrane thickness increased slightly. Also, Tamoxifen induce ordering of the hydrocarbon chains in DPPC bilayer. Analysis of MD trajectories shows that neutral Tamoxifen is predominantly found in the hydrophobic tail region, whereas protonated Tamoxifen is located at the lipid-water interface (polar region of DPPC lipid bilayers).
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Nanomedicine is a branch of medicine using nanotechnology to prevent and treat diseases. Nanotechnology represents one of the most effective approaches in elevating a drug‘s treatment efficacy and reducing toxicity by improving drug solubility, altering biodistribution, and controlling the release. The development of nanotechnology and materials has brought a profound revolution to medicine, significantly affecting the treatment of various major diseases such as cancer, injection, and cardiovascular diseases. Nanomedicine has experienced explosive growth in the past few years. Although the clinical transition of nanomedicine is not very satisfactory, traditional drugs still occupy a dominant position in formulation development, but increasingly active drugs have adopted nanoscale forms to limit side effects and improve efficacy. The review summarized the approved nanomedicine, its indications, and the properties of commonly used nanocarriers and nanotechnology.
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Numerous drugs have emerged to treat various diseases, such as COVID-19, cancer, and protect human health. Approximately 40% of them are lipophilic and are used for treating diseases through various delivery routes, including skin absorption, oral administration, and injection. However, as lipophilic drugs have a low solubility in the human body, drug delivery systems (DDSs) are being actively developed to increase drug bioavailability. Liposomes, micro-sponges, and polymer-based nanoparticles have been proposed as DDS carriers for lipophilic drugs. However, their instability, cytotoxicity, and lack of targeting ability limit their commercialization. Lipid nanoparticles (LNPs) have fewer side effects, excellent biocompatibility, and high physical stability. LNPs are considered efficient vehicles of lipophilic drugs owing to their lipid-based internal structure. In addition, recent LNP studies suggest that the bioavailability of LNP can be increased through surface modifications, such as PEGylation, chitosan, and surfactant protein coating. Thus, their combinations have an abundant utilization potential in the fields of DDSs for carrying lipophilic drugs. In this review, the functions and efficiencies of various types of LNPs and surface modifications developed to optimize lipophilic drug delivery are discussed.
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Liposomes with enhanced elasticity have been proven to increase the efficiency of drug transport across the skin. The understanding of the background physicochemical processes driving the liposome viscoelastic properties is an essential feature for the design of effective formulations involving different lipids and additive molecules. In this work we use field-cycled nuclear magnetic resonance relaxometry to analyze both the mechanical properties of liposome membranes, and their relationship with the involved molecular dynamics. Different liposomal formulations were considered. We show a correlation between the molecular dynamical regime and mesoscopic physical parameters that define the expected deformability of the vesicles. Results strongly suggest that the purity of the used lipids may influence the elastic properties of the membranes in an appreciable way. Common features in the behaviour of the involved dynamic variables were identified by comparing formulations with surfactants of similar molecular weight.
Book
Taurine, or 2-aminoethanesulfonic acid, is one of the most abundant sulfur-containing amino acids in the human body. It is found in the heart, brain, retina, and skeletal muscles, and is synthesized in the pancreas. Studies have revealed that taurine is of high physiological importance: it protects against pathologies associated with mitochondrial diseases, and linked processes like aging, metabolic syndrome, cancer, cardiovascular diseases, and neurological disorders. It is also used as a nutritional supplement. Taurine and the Mitochondrion: Applications in the Pharmacotherapy of Human Diseases explores the significance of taurine in the biology of mitochondria. It also explains its role as a pharmacological agent for treating different diseases. Readers will gain an insight into the crucial role it plays in human physiology and the benefits of taurine supplements. Topics covered in this reference include - Synthesis of taurine and its dietary sources - The Role of taurine in mitochondrial health - Taurine as a neurotransmitter - Beneficial effects of taurine in physiological systems such as the reproductive system, renal system, and the gastrointestinal tract - Hepatoprotective and anti-inflammatory properties of taurine - The anti-aging promise of taurine supplementation - Role of taurine supplementation in obesity
Chapter
As repeatedly mentioned in the current book, taurine (TAU) is a very hydrophilic molecule. Hence, the passage of this amino acid through the physiological barriers (e.g., blood-brain barrier; BBB) is weak. In this context, experimental and clinical studies that mentioned the positive effects of TAU on CNS disorders administered a high dose of this amino acid (e.g., 12 g/day). For example, in an animal model of hepatic encephalopathy, we administered 1 g/kg of TAU to hyperammonemic rats to preserve their brain energy status and normalize their locomotor activity. In some cases, where anticonvulsant effects of TAU were evaluated; also, a high dose of this amino acid was used (150 mg/kg). In other circumstances, such as investigations on the reproductive system, the blood-testis barrier (BTB) could act as an obstacle to the bioavailability of TAU. On the other hand, recent studies mentioned the importance of targeted delivery of molecules to organelles such as mitochondria. These data mention the importance of appropriate formulations of this amino acid to target brain tissue as well as cellular mitochondria. Perhaps, TAU failed to show significant and optimum therapeutic effects against human disease (e.g., neurological disorders) because of its inappropriate drug delivery system. Therefore, targeting tissues such as the brain with appropriate TAU-containing formulations is critical. The current chapter discusses possible formulations for bypassing physiological barriers (e.g., blood-brain barrier; BBB or BTB) and effectively targeting subcellular compartments with TAU. These data could help develop effective formulations for managing human diseases (e.g., CNS disorders or infertility issues in men).
Chapter
Solid lipid nanoparticlesSolid lipid nanoparticles (SLNs) are promising carriers that allow for the delivery of poorly water-soluble drugs and have the potential to achieve sustained drug release or targetedTargeted delivery to the site of interest. Here we describe the preparation of solid lipid nanoparticlesSolid lipid nanoparticles (SLNs) by forming a microemulsionMicroemulsions at an elevated temperature which, upon cooling, yields a suspension of solid nanoparticlesNanoparticles. This nanotemplate engineering method is inexpensive, reproducible, and easy to scale up.
Chapter
Atomic force microscopyAtomic force microscopy is a high-resolution and nonoptical technique used to visualize and characterize biological samples and surfaces. In pharmaceutical research and development (R&D) and quality control (QC), drug deliveryDrug delivery systems, like liposomesLiposomes with sizes in a nanometer range, are preferred samples to be studied through atomic force microscopy. The instrument can determine the sample’s topography (e.g., height), morphology, and material properties (e.g., hardness, adhesiveness). Various measuring modes, e.g., intermittent contact (AC mode), can generate height (measured), lock-in amplitude, and lock-in phase data, revealing interesting details about the drug deliveryDrug delivery system. In this study, empty and drug-loaded liposomesLiposomes with various lipidLipids compositions and sizes (50–800 nm) were visualized and characterized with state-of-the-art atomic force microscope (AFM)Atomic force microscopy (AFM). The main focus here was the preparation methods of the samples, instrumental settings, and pitfalls that can occur during the whole imagingImaging process. Moreover, troubleshooting and postdata processing are essential for a high-quality outcome.
Chapter
Nanotechnology is an emerging field in the drug delivery using the nanoparticles 5 to 200 nanometers in size. The drug is protected against chemical and enzymatic degradation by dissolving and entrapping the drug into biodegradable nanoparticles. The nanomaterials may be composed of proteins, polymers, polysaccharides, lipids, metals, etc. It is highly specific and target oriented. They have very low side effects, protects the drug from degradation, and a smaller number of doses required. The ultimate goal of nanodrug delivery system is to develop clinically useful formulation for treating diseases in patients. In this review article, we have discussed about the different types of nanotechnology‐based materials used in the drug delivery like liposomes, dendrimers, micelles their properties and applications. But the toxicity of the nanoparticles is of much health concern, which should be resolved.
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Since the progression of osteoarthritis (OA) is closely associated with synovitis and cartilage destruction, the inhibition of inflammatory responses in synovial macrophages and reactive oxygen species (ROS) induced apoptosis in chondrocytes is crucial for OA amelioration. However, most of the current anti-inflammatory and antioxidant drugs are small molecules apt to be eliminated in vivo. Herein, mesoporous polydopamine nanoparticles (DAMM NPs) doped with arginine and manganese (Mn) ions were prepared to load dexamethasone (DEX) for OA intervention. A series of in vitro studies showed that the sustained release of DEX from DAMM NPs suppressed synovial inflammation and simultaneously inhibited toll-like receptor 3 (TLR-3) production in chondrocytes, contributing to prevention of chondrocyte apoptosis through the inflammatory factor-dependent TLR-3/NF-κB signaling pathway via modulation of macrophage-chondrocyte crosstalk. In addition, DAMM NPs exerted a predominant role in removal of ROS generated in chondrocytes. Therefore, the DEX-loaded DAMM NPs significantly attenuated OA development in mice model. Importantly, the T1-T2 magnetic contrast capabilities of DAMM NPs allowed an MRI-trackable delivery, manifesting a distinct feature widely regarded to boost the potential of nanomedicines for clinical applications. Together, our developed antioxidant-enhanced DAMM NPs with MRI-visible signals may serve as a novel multifunctional nanocarriers for prevention of OA progression.
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The application of liposomes to assist drug delivery has already had a major impact on many biomedical areas. They have been shown to be beneficial for stabilizing therapeutic compounds, overcoming obstacles to cellular and tissue uptake, and improving biodistribution of compounds to target sites in vivo. This enables effective delivery of encapsulated compounds to target sites while minimizing systemic toxicity. Liposomes present as an attractive delivery system due to their flexible physicochemical and biophysical properties, which allow easy manipulation to address different delivery considerations. Despite considerable research in the last 50 years and the plethora of positive results in preclinical studies, the clinical translation of liposome assisted drug delivery platforms has progressed incrementally. In this review, we will discuss the advances in liposome assisted drug delivery, biological challenges that still remain, and current clinical and experimental use of liposomes for biomedical applications. The translational obstacles of liposomal technology will also be presented.
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This single-arm Phase II trial was designed to assess the safety and efficacy of pegylated liposomal doxorubicin and carboplatin combination chemotherapy in patients with platinum-sensitive recurrent ovarian cancer. Patients with a histological diagnosis of epithelial ovarian, fallopian tube or primary peritoneal carcinoma, who were relapse-free at least 6 months after completion of first-line platinum-based chemotherapy, and who had measurable disease and gave consent to participate in this study received infusions of pegylated liposomal doxorubicin (30 mg/m(2)) at 1 mg/min, followed by carboplatin (AUC 5 mg min/ml) over 30 min every 28 days. Thirty-three of 35 enrolled patients were eligible for efficacy analysis. One patient (3.0%) achieved a complete response, while 16 (48.5%) achieved a partial response, with an overall objective response rate of 51.5% (95% confidence interval, 34.5-68.6%). Among the 22 patients who had evaluable CA125 levels at entry, responses were observed in 18 patients, with a response rate of 81.8% (95% confidence interval, 65.3-98.3%). The median progression-free survival and overall survival rates for all 35 patients were 10.7 months (95% confidence interval, 8.1-13.2 months) and 38.8 months (95% confidence interval, 31.0-46.7 months), respectively. The most frequent Grade 3-4 toxicities, regardless of cause, were neutropenia (82.9%), thrombocytopenia (51.4%), leukopenia (45.7%) and anemia (17.1%). The safety and efficacy of pegylated liposomal doxorubicin and carboplatin combination chemotherapy in patients with platinum-sensitive recurrent ovarian cancer were confirmed. Although there were concerns of severe hematological toxicity with this therapy, this potential complication was safely managed through adequate monitoring of bone marrow function. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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Pegylation of nanoparticles has been widely implemented in the field of drug delivery to prevent macrophage clearance and increase drug accumulation at a target site. However, the shielding effect of polyethylene glycol (PEG) is usually incomplete and transient, due to loss of nanoparticle integrity upon systemic injection. Here, we have synthesized unique PEG-dendron-phospholipid constructs that form super stealth liposomes (SSLs). A β-glutamic acid dendron anchor was used to attach a PEG chain to several distearoyl phosphoethanolamine lipids, thereby differing from conventional stealth liposomes where a PEG chain is attached to a single phospholipid. This composition was shown to increase liposomal stability, prolong the circulation half-life, improve the biodistribution profile and enhance the anticancer potency of a drug payload (doxorubicin hydrochloride). Copyright © 2014. Published by Elsevier B.V.
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To evaluate the safety and efficacy of ketoprofen in Transfersome® gel (IDEA-033) in comparison with a ketoprofen-free vehicle (TDT 064) for the treatment of osteoarthritis (OA) of the knee. Patients with knee OA (N = 866) were randomly assigned to receive topical IDEA-033 containing 100, 50, or 25 mg ketoprofen, or TDT 064 twice daily for 12 weeks, in a double-blind trial. The primary efficacy endpoint was the change in the Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index pain subscale score. The coprimary efficacy endpoints were the WOMAC function subscale score and the patient global assessment of response to therapy. The secondary endpoints included the numeric pain rating for the first 14 days of treatment and the Outcome Measures in Rheumatology (OMERACT)-Osteoarthritis Research Society International (OARSI) responder rates. The WOMAC pain scores were reduced by approximately 50% or more in all four groups. The 100 and 50 mg ketoprofen groups, but not the 25 mg group, showed a superior reduction in the WOMAC pain score versus the TDT 064 group (100 mg: -57.4% [P = 0.0383]; 50 mg: -57.1% [P = 0.0204]; and 25 mg: -53.4% [P = 0.3616] versus TDT 064: -49.5%). The superiority of the ketoprofen-containing formulations was not demonstrated for the WOMAC function subscale score, whereas the patient global assessment of 50 mg ketoprofen group, but not the 100 or 25 mg group, was superior to that of the TDT 064 group (P = 0.0283). Responder rates were significantly higher for all the IDEA-033 groups versus the TDT 064 group, but were high in all groups (100 mg: 88.6%; 50 mg: 86.8%; 25 mg: 88.6%; and TDT 064: 77.5%). Dermal reactions were the only relevant drug-related adverse events in all four groups. The 50 and 100 mg ketoprofen doses of IDEA-033 were only marginally superior to TDT 064 for reducing pain associated with knee OA. The study indicates a high treatment response to the topical ketoprofen-free vehicle TDT 064.
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The field of cancer nanomedicine is considered a promising area for improved delivery of bioactive molecules including drugs, pharmaceutical agents and nucleic acids. Among these, drug delivery technology has made discernible progress in recent years and the areas that warrant further focus and consideration towards technological developments have also been recognized. Development of viable methods for on-demand spatial and temporal release of entrapped drugs from the nanocarriers is an arena that is likely to enhance the clinical suitability of drug-loaded nanocarriers. One such approach, which utilizes light as the external stimulus to disrupt and/or destabilize drug-loaded nanoparticles, will be the discussion platform of this article. Although several phototriggerable nanocarriers are currently under development, I will limit this review to the phototriggerable liposomes that have demonstrated promise in the cell culture systems at least (but not the last). The topics covered in this review include (i) a brief summary of various phototriggerable nanocarriers; (ii) an overview of the application of liposomes to deliver payload of photosensitizers and associated technologies; (iii) the design considerations of photoactivable lipid molecules and the chemical considerations and mechanisms of phototriggering of liposomal lipids; (iv) limitations and future directions for in vivo, clinically viable triggered drug delivery approaches and potential novel photoactivation strategies will be discussed.
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To describe the preparation of nano emodin transfersome (NET) and investigate its effect on mRNA expression of adipose triglyceride lipase (ATGL) and G0/G1 switch gene 2 (G0S2) in adipose tissue of diet-induced obese rats. NET was prepared by film-ultrasonic dispersion method. The effects of emodin components at different ratios on encapsulation efficiency were investigated.The NET envelopment rate was determined by ultraviolet spectrophotometry. The particle size and Zeta potential of NET were evaluated by Zetasizer analyzer. Sixty male SD rats were assigned to groups randomly. After 8-week treatment, body weight, wet weight of visceral fat and the percentage of body fat (PBF) were measured. Fasting blood glucose and serum lipid levels were determined. The adipose tissue section was HE stained, and the cellular diameter and quantity of adipocytes were evaluated by light microscopy. The mRNA expression of ATGL and G0S2 from the peri-renal fat tissue was assayed by RT-PCR. The appropriate formulation was deoxycholic acid sodium salt vs. phospholipids 1:8, cholesterol vs. phospholipids 1:3, vitamin Evs. phospholipids 1:20, and emodin vs. phospholipid 1:6. Zeta potential was -15.11 mV, and the particle size was 292.2 nm. The mean encapsulation efficiency was (69.35 +/- 0.25)%. Compared with the obese model group, body weight, wet weight of visceral fat, PBF and mRNA expression of G0S2 from peri-renal fat tissue were decreased significantly after NET treatment (all P < 0.05), while high-density lipoprotein cholesterol (HDL-C), the diameter of adipocytes and mRNA expression of ATGL from peri-renal fat tissue were increased significantly (all P < 0.05). The preparation method is simple and reasonable. NET with negative electricity was small and uniform in particle size, with high encapsulation efficiency and stability. NET could reduce body weight and adipocyte size, and this effect was associated with the up-regulation of ATGL, down-regulation of G0S2 expression in the adipose tissue, and improved insulin sensitivity.
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Sustained delivery of analgesic agents at target sites remains a critical issue for effective pain management. The use of nanocarriers has been reported to facilitate effective delivery of these agents to target sites while minimizing systemic toxicity. These include the use of biodegradable liposomal or polymeric carriers. Of these, liposomes present as an attractive delivery system due to their flexible physicochemical properties which allow easy manipulation in order to address different delivery considerations. Their favorable toxicity profiles and ease of large scale production also make their clinical use feasible. In this review, we will discuss the concept of using liposomes as a drug delivery carrier, their in vitro characteristics as well as in vivo behavior. Current advances in the targeted liposomal delivery of analgesic agents and their impacts on the field of pain management will be presented.
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The aim of this study was to prepare and investigate the potential use of liposomes in the transdermal drug delivery of meloxicam (MX). The vesicles containing a constant amount of MX, phosphatidylcholine (PC), cholesterol (Chol) and cetylpyridinium chloride (CPC) (1:5:1:1 MX/PC/Chol/CPC molar ratio) to obtain liposomes. MX loaded liposomes were investigated for particle size, zeta potential, entrapment efficiency (%EE) and in vitro skin permeation. The results indicated that the liposomes were spherical in structure, 77 to 100 nm in size and charged. The %EE of MX in the vesicles ranged from 55 to 56%. The elastic liposomes consisting of MX/PC/Chol/CPC provided a significantly higher skin permeation of MX compared to the other formulations. Fourier Transform Infrared Spectroscopy (FT-IR) and Differential Scanning Calorimetry (DSC) analysis indicated that the application of liposomes may disrupt the stratum corneum lipid. Our research suggests that MX loaded elastic liposomes can be potentially used as a transdermal drug delivery system.
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Abstract Liposomes are well known lipid carriers for drug delivery of bioactive molecules encapsulated inside their membrane. Liposomes as skin drug delivery systems were initially promoted primarily for localized effects with minimal systemic delivery. Subsequently, a novel vesicular system, transferosomes was reported for transdermal delivery with efficiency similar to subcutaneous injection. The multiple bilayered organizations of lipids applied in these vesicles structure are somewhat similar to complex nature of stratum corneal intercellular lipids domains. The incorporation of novel agents into these lipid vesicles results in the loss of entrapped markers but it is similar to fluidization of stratum corneum lipids on treatment with a penetration enhancer. This approach generated the utility of penetration enhancers/fluidizing agents in lipids vesicular systems for skin delivery. For the transdermal and topical applications of liposomes, fluidity of bilayer lipid membrane is rate limiting which governs the permeation. This article critically reviews the relevance of using different types of vesicles as a model for skin in permeation enhancement studies. This study has also been designed to encompass all enhancement measurements and analytical tools for characterization of permeability in liposomal vesicular system.
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