Vesicular Delivery Systems Research Articles

Novel Vesicular Bilosomal Delivery Systems for Dermal/Transdermal Applications.

The application of therapeutically active molecules through the dermal/transdermal route into the skin has evolved as an attractive formulation strategy in comparison to oral delivery systems for the treatment of various disease conditions. However, the delivery of drugs across the skin is limited due to poor permeability. Dermal/transdermal delivery is associated with ease of accessibility, enhanced safety, better patient compliance, and reduced variability in plasma drug concentrations. It has the ability to bypass the first-pass metabolism, which ultimately results in steady and sustained drug levels in the systemic circulation. Vesicular drug delivery systems, including bilosomes, have gained significant interest due to their colloidal nature, improved drug solubility, absorption, and bioavailability with prolonged circulation time for a large number of new drug molecules. Bilosomes are novel lipid vesicular nanocarriers comprising bile salts, such as deoxycholic acid, sodium cholate, deoxycholate, taurocholate, glycocholate or sorbitan tristearate. These bilosomes are associated with high flexibility, deformability, and elasticity attributed to their bile acid component. These carriers are advantageous in terms of improved skin permeation, increased dermal and epidermal drug concentration, and enhanced local action with reduced systemic absorption of the drug, resulting in reduced side effects. The present article provides a comprehensive overview of the biopharmaceutical aspects of dermal/transdermal bilosome delivery systems, their composition, formulation techniques, characterization methods, and applications.

Vesicle delivery systems of functional substances for precision nutrition.

Vesicular delivery systems are highly ordered assemblies consisting of one or more concentric bilayers formed by the self-assembly of amphiphilic building blocks in the presence of water. In the field of functional food, vesicular delivery systems have been widely explored for effective formulations to deliver functional substances. With the effort of scientific research, certain categories of vesicular delivery systems have successfully been translated from the laboratory to the global market of functional food. This chapter aims to present comprehensively the various vesicular delivery systems, including their design, preparation methods, encapsulation of functional substances, and application in nutritional interventions.

Review on novel targeted enzyme drug delivery systems: enzymosomes.

The goal of this review is to present enzymosomes as an innovative means for site-specific drug delivery. Enzymosomes make use of an enzyme's special characteristics, such as its capacity to accelerate the reaction rate and bind to a particular substrate at a regulated rate. Enzymosomes are created when an enzyme forms a covalent linkage with a liposome or lipid vesicle surface. To construct enzymosomes with specialized activities, enzymes are linked using acylation, direct conjugation, physical adsorption, and encapsulation techniques. By reducing the negative side effects of earlier treatment techniques and exhibiting efficient medication release, these cutting-edge drug delivery systems improve long-term sickness treatments. They could be a good substitute for antiplatelet medication, gout treatment, and other traditional medicines. Recently developed supramolecular vesicular delivery systems called enzymosomes have the potential to improve drug targeting, physicochemical characteristics, and ultimately bioavailability in the pharmaceutical industry. Enzymosomes have advantages over narrow-therapeutic index pharmaceuticals as focusing on their site of action enhances both their pharmacodynamic and pharmacokinetic profiles. Additionally, it reduces changes in normal enzymatic activity, which enhances the half-life of an enzyme and accomplishes enzyme activity on specific locations.

Niosomal-Based Drug Delivery Platforms: A Promising Therapeutic Approach to Fight Staphylococcus aureus Drug Resistance

Staphylococcus aureus, a prominent bacterial pathogen, presents formidable medical challenges owing to its rapid development of resistance. The emergence of multidrug resistant (MDR) S. aureus strains has become a pressing concern for healthcare systems, driving researchers to explore novel therapeutic strategies for managing infections associated with this pathogen. In this pursuit, niosomal-based platforms have emerged as promising candidates to effectively target S. aureus and fight conventional antimicrobial resistance. Niosomes comprise a bilayer membrane formed by nonionic surfactants, which can encapsulate both hydrophilic and hydrophobic drugs. These nanoparticles are known as vesicular delivery systems and have many advantages, such as low cost, less toxicity, and more flexibility and stability. Moreover, niosomes, being an effective drug delivery system, can directly interact with the bacterial cell envelope, thereby enhancing the pharmacokinetic activities of drugs at infected sites. A niosome-based delivery system can effectively treat S. aureus infections by destroying the biofilm community, increasing intracellular targeting, and enhancing the antibacterial activity. The main mechanisms of action of niosomes against resistant S. aureus strains involve the ability to resist enzymatic degradation, controlled release profile, and targeted drug delivery, which can provide an effective dosage of antimicrobial agents at the site of actions. In addition, niosomes have the potential to transfer wide-spectrum materials from different classes of antibiotics to nonantibiotic antimicrobial agents, such as natural compounds, antimicrobial peptides, and metallic nanoparticles. The combination of polymeric materials in the structure of a niosomal formulation could improve their bioavailability, loading capacity, and therapeutic efficacy for different applications. Furthermore, niosomes could find application in photodynamic therapy, offering a promising alternative to conventional treatments for eradicating drug-resistant S. aureus isolates. Finally, niosomal nanocarriers can be developed for delivering the drugs to desired sites by different routes of administration and could be considered a powerful strategy for overcoming the therapeutic obstacles caused by MDR S. aureus.

A Mini-review Based on Multivesicular Liposomes: Composition, Design, Preparation, Characteristics, and Therapeutic Importance as DEPOFOAM® Technology.

Vesicular delivery systems are a kind of drug delivery system that is gaining popularity due to its sustained release nature. This article was designed to understand the characteristics of a drug carrier called multivesicular liposomes, which have the potential to be the future of sustainedrelease drug delivery systems. Multivesicular liposomes have a honeycomb-like structure made up of non-concentric aqueous polyhedral compartments separated by continuous lipid membranes. Because of their unusual structure, they can encapsulate both hydrophilic and lipophilic pharmaceuticals and release them in a prolonged and controlled manner. They also have high encapsulation efficiency, bioavailability, biocompatibility, and stability, and are biodegradable by nature, making them suitable for treating chronic disorders. Encapsulating drugs into multivesicular liposomes is called DepoFoam® technology, which has the capability to release them in a timely manner, lowering the drug administration frequency. As a result, the FDA has approved several various approaches for this technology to treat chronic conditions. Multivesicular liposomes in the form of DepoFoam® technology hold a promising future as a novel drug delivery system. Much research needs to be done to extend their use across various aspects of the therapeutic field.

Vesicular drug delivery systems for oral absorption enhancement

Oral administration is the most acceptable route of drug delivery at this stage due to its convenience, safety, and non-invasiveness. However, drugs given orally are exposed to a complex gastrointestinal environment, causing a tremendous challenge for their successful absorption into the circulation. Over the past decades, researchers have developed various novel pharmaceutical technologies to improve oral absorption, among which the vesicular drug delivery system (like liposomes, niosomes and transfersomes) has received extensive attention. Encouragingly, there have been several investigations confirming the improved effect of vesicular drug delivery systems on oral drug absorption. Nevertheless, the clinical translation of oral vesicular drug delivery systems has been less impressive than implied by the positive results, and few vesicular formulations for oral use have been marketed yet. Against this background, this article provides an overview of the current applications and challenges associated with the vesicular delivery systems available for oral drug delivery, specifically liposomes, niosomes, transfersomes, chitosomes and bilosomes. The composition, formation mechanism, drug delivery advantages and application cases of these carriers in oral drug delivery are summarized. The possible mechanisms by which vesicular carriers enhance oral drug absorption are analyzed in terms of the in vivo process of oral drugs. Further, the challenges that oral vesicular carriers now face, such as safety, undefined in vivo fate, and scale-up production, are summarized, while possible strategies to deal with them are indicated. By reviewing the aforementioned, it can facilitate a more comprehensive knowledge of vesicular systems that can be used for oral drug delivery, providing a theoretical basis and reference for the design of oral formulations.

Properties and cellular uptake of photo-triggered mixed metallosurfactant vesicles intended for controlled CO delivery in gas therapy

The scientific relevance of carbon monoxide has increased since it was discovered that it is a gasotransmitter involved in several biological processes. This fact stimulated research to find a secure and targeted delivery and lead to the synthesis of CO-releasing molecules. In this paper we present a vesicular CO delivery system triggered by light composed of a synthetized metallosurfactant (TCOL10) with two long carbon chains and a molybdenum-carbonyl complex. We studied the characteristics of mixed TCOL10/phosphatidylcholine metallosomes of different sizes. Vesicles from 80 to 800 nm in diameter are mainly unilamellar, do not disaggregate upon dilution, in the dark are physically and chemically stable at 4 °C for at least one month, and exhibit a lag phase of about 4 days before they show a spontaneous CO release at 37 °C. Internalization of metallosomes by cells was studied as function of the incubation time, and vesicle concentration and size. Results show that large vesicles are more efficiently internalized than the smaller ones in terms of the percentage of cells that show TCOL10 and the amount of drug that they take up. On balance, TCOL10 metallosomes constitute a promising and viable approach for efficient delivery of CO to biological systems.

Chlorogenic acid loaded niosomes and proniosomes: in vitro antioxidant and antibacterial activities with efficacy in wound healing

ObjectiveTo develop and optimize niosomal and proniosomal vesicular delivery systems for a naturally occurring polyphenol chlorogenic acid (CGA), so as to improve its physicochemical properties and permeability, which may enhance its pharmacological activity. MethodsThe formulated CGA niosomes (CGANs) and CGA proniosomes (CGAPNs) were primed by thin film hydration and phase separation coacervation methods, and were characterized with different attributes including particle size, morphology, entrapment efficiency, zeta potential, deformability, in vitro diffusion, ex vivo permeability, and long-term stability. Their efficiency was further evaluated with in vitro antioxidant assay, antibacterial assays, and excision wound healing model in rats. ResultsOptimized CGANs and CGAPNs showed spherical vesicles with particle size of 490.1 ± 43.0 and 280.0 ± 22.0 nm, polydispersity index (PDI) values of 0.526 and 0.173, and stable zeta potential values of - 29.3 ± 6.4 and - 33.2 ± 6.5 mV, respectively. The CGANs and CGAPNs vesicles showed higher entrapment (98.27% ± 0.46% & 97.27% ± 0.25%) with good deformability (8.77 ± 0.22 & 6.87 ± 0.17), higher in vitro diffusion (97.96% ± 1.67% & 91.00% ± 1.32%), and permeability coefficient values (67 × 10-3 ± 1.72 & 52 × 10-3 ± 1.09) with long-term stability in comparison with plain CGA. Enhanced 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and Fe2 + chelation ability was obtained with CGAPNs > CGANs. They also demonstrated lethal bactericidal activity on different gram positive and gram negative strains with lower minimum inhibitory concentration (MIC) values (8 × and 16 × times less) as compared with plain CGA. Significant reduction (P < 0.05) in wound area with higher wound contraction percentages on day 9 was observed with CGANPs (99.56%) > CGANs (98.44%) in comparison with marketed (92.89%) and CGA (88.89%) hydrogel. ConclusionThese results show great potential of CGANs and CGAPNs for topical wound healing application. This is the first study of CGA in niosomal and proniosomal topical delivery systems.

Aquasomes: Advanced Vesicular-based Nanocarrier Systems.

Aquasomes are novel trilayered non-lipoidal vesicular nanocarriers that demonstrate structural similarity to ceramic nanoparticles with theranostic activity for diseases like ovarian cancer and antigen delivery. The objective of the present article is to highlight the multifaceted potential of aquasomes over other nanocarriers for the treatment of various treatments like hemophilia A, cancer, and hepatitis. Aquasomes enter the target cell by modifying the surface chemistry, extending drug release. The solid core of aquasomes provides structural stability whereas their oligomeric coatings protect drugs from dehydration. This vesicular delivery system was successfully utilized for the delivery of acid-labile enzymes, antigens, vaccines, etc. The aquasomes nanocarrier exhibits a larger surface area, volume, and mass ratio that allows the drug to penetrate inside the cells and a prolonged drug release profile. Moreover, aquasomes consist of a high mechanical strength, reduced or no biodegradability during storage, and a good body response that facilitates deeper penetration into capillaries which makes them more special and interesting. Aquasomes are a potential alternative over other nanocarriers for insulin, antigen, and oxygen delivery. In the near future, aquasomes-based nano-drug delivery systems can be a fascinating field for research in nanotechnology.

Transferosome: A Vesicular Transdermal Delivery System for Enhanced Drug Permeation

The barrier function of the skin limits transdermal medication delivery. Vesicular systems are one of the most contentious mechanisms for delivering active compounds transdermally. The discovery of elastic vesicles such transferosomes, ethosomes, cubosomes, phytosomes, and others reignited interest in creating transdermal delivery systems. Vesicular drug delivery systems are highly organised assemblies made up of one or more concentric bilayers that form when amphiphilic building units self-assemble in water. Because of their potential to localise drug activity at the site or organ of action while reducing its concentration at other places in the body, vesicular drug delivery systems are particularly significant for targeted drug delivery. The vesicular drug delivery system keeps drug activity at a specified rate, keeps drug levels in the body reasonably constant (zero order kinetics), and reduces unwanted side effects at the same time. It can also target medication delivery utilizing carriers or chemical derivatization to localise drug action in the affected tissue or organ. Vesicular drug delivery systems have been used to improve The therapeutic index, solubility, stability, and rapid degradation of a pharmacological molecule are all important factors to consider. As a result, a number of innovative vesicular drug delivery systems that allow drug targeting and prolonged or regulated drug release have been produced. This review will focus on diverse lipoidal and non-lipoidal vesicles, with a special emphasis on pharmaceutical targeting.

Colloidal and vesicular delivery system for herbal bioactive constituents.

The main objective of the present review is to explore and examine the effectiveness of currently developed novel techniques to resolve the issues which are associated with the herbal constituents/extract. A systematic thorough search and collection of reviewed information from Science direct, PubMed and Google Scholar databases based on various sets of key phrases have been performed. All the findings from these data have been studied and briefed based on their relevant and irrelevant information. Herbal drugs are gaining more popularity in the modern world due to their applications in curing various ailments with minimum toxic effects, side effect or adverse effect. However, various challenges exist with herbal extracts/plant actives such as poor solubility (water/lipid), poor permeation, lack of targeting specificity, instability in highly acidic pH, and liver metabolism, etc. Nowadays with the expansion in the technology, novel drug delivery system provides avenues and newer opportunity towards the delivery of herbal drugs with improved physical chemical properties, pharmacokinetic and pharmacodynamic. Developing nano-strategies like Polymeric nanoparticles, Liposomes, Niosomes, Microspheres, Phytosomes, Nanoemulsion and Self Nano Emulsifying Drug Delivery System, etc. imparts benefits for delivery of phyto formulation and herbal bioactives. Nano formulation of phytoconstituents/ herbal extract could lead to enhancement of aqueous solubility, dissolution, bioavailability, stability, reduce toxicity, permeation, sustained delivery, protection from enzymatic degradation, etc. CONCLUSION: Based on the above findings, the conclusion can be drawn that the nano sized novel drug delivery systems of herbal and herbal bioactives have a potential future for upgrading the pharmacological action and defeating or overcoming the issues related with these constituents. The aims of the present review was to summarize and critically analyze the recent development of nano sized strategies for promising phytochemicals delivery systems along with their therapeutic applications supported by experimental evidence and discussing the opportunities for further aspects.

Vesicular drug delivery for the treatment of topical disorders: current and future perspectives.

Vesicular drug delivery has become a useful approach for therapeutic administration of pharmaceutical compounds. Lipid vesicles have found application in membrane biology, immunology, genetic engineering and theragnostics. This review summarizes topical delivery, specifically dermal/transdermal, ocular and transungual, via these vesicles, including future formulation perspectives. Liposomes and their subsequent derivatives, viz. niosomes, transferosomes, pharmacososmes and ethosomes, form a significant part of vesicular systems that have been successfully utilized in treating an array of topical disorders. These vesicles are thought to be a safe and effective mode of improving the delivery of lipophilic and hydrophilic drugs. Several drug molecules are available for topical disorders. However, physicochemical properties and undesirable toxicity have limited their efficacy. Vesicular delivery systems have the potential to overcome these shortcomings due to properties such as high biocompatibility, simplicity of surface modification and suitability as controlled delivery vehicles. However, incorporating these systems into environmentally responsive dispersants such as hydrogels, ionic liquids and deep eutectic solvents may further enhance therapeutic prowess of these delivery systems. Consequently, improved vesicular drug delivery can be achieved by considering combining some of these formulation approaches.

A Review on Novel vesicular systems for enhanced Oral bioavailability of Lipophilic drugs

The poor oral bioavailability of many drugs is mainly due to the poor aqueous solubility, chemical instability and pre-absorptive metabolism. Numerous approaches have been developed for enhancement of oral bioavailability and were currently in the clinical application. Even though, some drugs not meet the required clinical application due to the patient compliance and ineffective therapeutic levels. Vesicular delivery systems are considered as alternative delivery for the enhancement the bioavailability of this category of drugs. The enhanced bioavailability of the liphophilic drugs from the vesicular systems mainly due to the increased effective surface area of the drug in the presence of lipids, surfactants and co surfactants, enhanced lymphatic uptake, altered gastric motility and by virtue of their small particle size. Extensive literature is available for the properties, applications, and preparation and evaluation methods. This review mainly dealt with the reported drug loaded various vesicular systems such as liposomes, niosomes, lipid nanoparticles, self-emulsifying delivery system, nanosuspensions.

NIOSOMES: CLASSIFICATION, PREPARATION AND APPLICATION

Vesicular medication delivery system, for instance, niosomes may be a novel medication delivery system, during which the answer is enclosed in vesicle which is formed by Non-ionic surfactant. Structurally, niosomes are almost like liposomes, therein they're also made from a bilayer. However, the bilayer within the case of niosomes is formed from non-ionic surface actives agents instead of phospholipids as seen just in case of liposomes. Niosomes tackled the difficulty of insolubility, instability, low bioavailability and fast debasement of medicines. The vesicular system of niosomes, with their bilayer structure assembled by nonionic surfactants, is in a position to reinforce the bioavailability of a drug to a predetermined area for a period. The both hydrophilic or lipophilic nature (amphiphilic nature) of niosomes increase their capacity in encapsulating lipophilic or hydrophilic drugs. Differents type additives, such as cholesterol, are often wont to maintain the rigidity of the niosomes structure. The basic aspects of niosomes, such as their structural components, methods of preparation, and current applications to various diseases.

Extracellular Vesicles Regulate Cancer Metastasis.

Metastatic cancer is a complex disease associated with poor prognosis and accounts for the majority of cancer related deaths. To date, many of the molecular mechanisms driving metastatic disease remain elusive and require further investigation for the development of effective treatment strategies. Recent studies have shown that extracellular vesicles (EVs) can be exploited by tumors to assist in cancer cell growth, proliferation, migration, invasion and metastasis. Cancer cells have proven efficient in educating fibroblasts, within their microenvironment, to secrete EVs as communicative vessels for mediating phenotypic changes in recipient cells. Using this vesicular delivery system, cancer cells can establish a new metastatic niche within distant sites, away from the primary tumor, thus favoring cancer progression. These findings demonstrate the availability of a new route for therapeutic intervention in the inhibition of cancer dissemination. Although, several approaches to target cancer cell secretion of EVs are detailed in the literature, there is still no defined way to currently apply them in clinical settings. Hence, further studies are required to unravel the molecular mechanisms of metastasis - governed by the establishment and release of cancer associated EVs.

Progress in novel ultradeformable vesicular drug carrier in the topical and transdermal treatment of psoriasis.

Psoriasis is a chronic autoimmune condition that is described by infected skin patches. Ultradeformable vesicles have been a novel carrier for the treatment of psoriasis in topical and transdermal therapy. The systemic route may induce adverse effects and the drug concentration may not be localized when applied topically to the psoriasis skin due to their physicochemical properties. These limitations can be overcome by a vesicular delivery system such as transferosomes. Research on transferosomes is ongoing. Transferosomes are flexible deformable vesicular structures, which consist of a bilayer softening agent such as an edge activator, which allows it to penetrate deeper dermal layers. This review outlines the use of transferosomes in the treatment of deeply rooted dermal disorders like psoriasis.

Skin cancer therapy: From conventional to nutraceutical based nanovesicular carriers

Skin cancer has one of the highest incidences of any type of cancer with an increasing incidence rate worldwide. It is life threatening and has led to immense economic and human loss all over the world. The conventional treatment strategies have profound adverse effects, which necessitated the development of novel methods. Nutraceuticals are naturally occurring compounds, and they were reported to exhibit great efficacy in cancer treatment and prevention. Accordingly, topical delivery of nutraceuticals can be considered the most optimum approach for efficient and safe treatment of skin cancer. However, the utmost challenge to topical drug delivery is the impermeable nature of the skin which hinders drug penetration/permeation. Hence, the use of vesicular delivery systems for nutraceuticals has been a chief research area for years. In this review, we overview skin cancer with its pathogenesis, conventional treatment strategies and the nano-carrier based approaches for the delivery of nutraceuticals through the skin.

Optimization of gallic acid-loaded transfersomes using a Box-Behnken factorial design

The pleiotropic activities of gallic acid have triggered the interest of researchers in the improvement of its poor bioavailability, such that this phenolic compound can be used for prophylactic and therapeutic purposes. At the same time, transfersomes have been reported to be valuable nanodelivery systems to boost the transdermal delivery of bioactive compounds. Thus, this study aims at optimizing a transfersomal formulation for the transdermal delivery of gallic acid using a Box-Behnken factorial design. This experimental design was successfully implemented and validated, yielding an optimized formulation with the desirable properties in terms of size, polydispersity index and loading capacity. Overall, this study opens up the possibility of efficiently delivering gallic acid to the deeper layers of skin in pharmaceutical and cosmetic formulations. Keywords: vesicular delivery systems, nanotechnology, phytochemicals, Box-Behnken.

Sphingosomes: A Novel Lipoidal Vesicular Drug Delivery System

Vesicular drug delivery system has various advantages thereby improving therapeutic efficacy and by sustaining and controlling action of drugs. Liposomes, sphingosomes, ethosomes, cubosomes, pharmacasomes, niosomes, transferosomes are the newly developed vesicular drug delivery system. This review article mainly deals with the sphingosomal drug delivery system. Sphingosomes are vesicular drug delivery systems in which an aqueous volume is enclosed with sphingolipid bilayer membranes. Sphingosomes has an enhanced area of interest because of their applicability in improving the in vivo delivery of various chemotherapeutic agents, biological macromolecules and diagnostics. Sphingosome has major advantages over other vesicular drug delivery systems like high stability, more in vivo circulation time, high tumor loading efficacy in case of cancer therapy as compared to liposomes, niosomes etc. Sphingosomes are clinically used vesicular delivery system for chemotherapeutic agent, biological macromolecule and diagnostics. This review concluded that sphingosome represents a promising vesicular drug delivery system for a range of possible therapeutic applications.

Thymoquinone-loaded ethosome with breast cancer potential: optimization, in vitro and biological assessment

Ethosomes are most commonly used vesicular delivery system compared to other lipidic vesicles due to its ethanolic content. Thymoquinone (TQ), the main biologically active complex of Black Cumin seed, has established anticancer activities in several tumors. In this work, the preparation of ethosome for TQ encapsulation by response surface method (RSM) was developed. Central composite design (CCD) was used to optimize three effective parameters involved in ethosome structure including phospholipid, cholesterol and ethanol concentration and the combined effects of them, as well. The obtained optimum values for the variables were phospholipid 5% (W/W), ethanol 45% (V/V) and cholesterol 1.5% (W/W) which were validated by experimental assay. The ethosomal formulation was more characterized for vesicle shape, size, zeta potential and entrapment efficiency percentage. The result showed an efficiency of 99% for drug entrapment with average vesicle size and zeta potential of 20 ± 1 nm and − 63 ± 2 mv, respectively. A quadratic model with a high adequacy (R2) for size and zeta potential of 0.9319 and 0.9338, respectively, was resulted from RSM and experimental assay. Thymoquinone (TQ) encapsulated in optimized ethosome. Also, cellular toxicity and release test was done. The toxicity and release curves were obtained and the cytotoxic activity of the ethosomic TQ against MCF-7 cell lines was greater than free TQ. IC50 values of free TQ, ethosomic TQ, were found to be 1.10 µg/ml, 0.95 µg/ml, respectively. The generated model suggests a new approach to prediction and experimental lipidic carriers.Graphic abstractCentral composite design (CCD) was used to optimize three effective parameters involved in ethosome structure including phospholipid, cholesterol and ethanol concentration and the combined effects of them, as well. The ethosomal formulation was more characterized for vesicle shape, size, zeta potential and entrapment efficiency percentage. Also, cellular toxicity and release test was done. The toxicity and release curves were obtained and the cytotoxic activity of the ethosomic TQ against MCF-7 cell lines was greater than free TQ.