Vesicular Carriers Research Articles

Proniosomal vesicles as an effective strategy to optimize naproxen transdermal delivery

The oral administration of naproxen, a non-steroidal analgesic, antipyretic, anti-inflammatory drug, is associated with various gastrointestinal side effects including peptic ulcer and gastritis. The objective of the present research was to evaluate the prospective of transdermal delivery of naproxen using proniosomes as a vesicular carrier and its comparison with oral therapy. Drug loaded proniosomes were prepared by coacervation phase separation, which comprising of spans/tweens, lecithin, and cholesterol. The influence of formulation components was evaluated to assess their impact on the entrapment efficiency, vesicle size, zeta potential, in vitro release and ex vivo permeation. The results signify that the type of surfactant influenced the entrapment efficiency, vesicle size and zeta potential values of prepared proniosomes. All formulations displayed nano-sized vesicles with small polydispersity index value showing narrow particle size distribution. Hydrophilic tweens produced larger vesicles and exhibited greater drug release than their hydrophobic spans counterparts. Prepared proniosomes exhibited distinct drug release profile (p < 0.05) as compared to control HPMC hydrogel. The proniosomal formulation (F3) containing span 60 showed superior transdermal flux (1.10 ± 0.24 μg cm−2 h−1) when compared to other non-ionic surfactants tested. In vivo data demonstrated both anti-inflammatory and antinociceptive efficiency of transdermal naproxen proniosome formulation (F3) was equivalent to the oral marketed naproxen tablets at same dose. Overall the results of present investigation suggest that proniosomes can be considered as a practicable and feasible alternative for oral naproxen delivery.

Formulation Development and Evaluation of Novel Vesicular Carrier for Enhancement of Bioavailability of Poorly Soluble Drug.

Niosomes are a vesicular carrier system comprised of a Nonionic surfactant bilayer surrounding an aqueous compartment. Niosomes are presumed to raise the intake of the poorly water-soluble drugs by M cells of Peyer's patches present in the intestine's lymphatic tissues, thereby avoiding the first-pass metabolism and increasing its oral bioavailability. Biodegradability, nonimmunogenic nature, minimal side effects, low cost, good stability, and flexibility to incorporate hydrophilic and lipophilic drugs are other advantages of niosomes. To formulate and evaluate a novel vesicular carrier system of a poorly soluble drug Lurasidone hydrochloride for the enhancement of its solubility and bioavailability. The thin-film hydration technique used to prepare Lurasidone hydrochloride loaded niosomes using different grades of nonionic surfactants like Brij, Span, and Tween. They evaluated for particle size, zeta potential, percent entrapment efficiency, in-vitro drug release, and in-vivo study. Niosomes comprised of Brij S-100 in drug: cholesterol: surfactant (1:1:1) showed particle size (1.15 ± 0.21 μm) and percent entrapment efficiency (97.02 ± 0.21%) and was selected for further studies. Various pharmacokinetic parameters like Cmax (281.27ng/ml), Tmax (5 h), and AUC (2640.197) were found to be significantly improved compared to plain drug solution. The Niosomal formulation could be the promising drug delivery system for the controlled and sustained release of Lurasidone.

Lipid Based Nanocarriers: Promising Drug Delivery System for Topical Application

AbstractLipid based delivery system is gaining significant attention of researchers working on the development of novel formulations for improved therapeutic efficacy and safety of drugs. Topical drug delivery is needed in treatment of skin, eyes, rectum, vagina disorders and systemic disorders having skin manifestations. Lipid nanocarriers have widespread application in the topical drug delivery due to the biocompatible, biodegradable, nontoxic and nonirritating nature of the lipid. Microemulsion and nanoemulsion contain lipids in the nanosize range which can lead to penetration of drug to the deeper skin layers. Solid lipid nanoparticles and nanolipid carriers act by forming an occlusive layer on the skin leading to increased hydration and penetration of the drug. Vesicular carriers such as liposomes, niosomes, ultradeformable vesicles, cubosomes etc. are also reported to enhance the penetration of the entrapped drugs in deeper layers of skin. These carrier systems are mainly composed of lipids, surfactants, and co‐surfactants which are safe and quite acceptable by regulatory authorities. The present review article focuses on different types of lipid nanocarriers used in topical drug delivery, their advantages and limitations, mechanism of enhanced penetration, work reported in the related literature, characterization tests and their safety and toxicity concerns.

Ultra-deformable vesicular carriers for enhanced Permeation of Drugs.

Ultra-deformable vesicular carriers for enhanced Permeation of Drugs.

FORMULATION DEVELOPMENT AND EVALUATION OF NIOSOMAL GEL OF TAZAROTENE FOR TREATMENT OF PSORIASIS

Aim of the current work was to prepare and characterize Tazarotene encapsulated niosome, incorporated in to a appropriate dermatological base and assess its comparative effectiveness in the cure of dermal infections. Drug encapsulated niosomes was formulated by thin film hydration method using different ratio of drug, cholesterol and surfactant ratio. Vesicular carriers were characterized for vesicle shape and size, drug entrapment efficiency, and in-vitro diffusion study. Vesicular size, zeta potential and drug entrapment efficiency of the optimized niosomes were determined. Microscopic examination suggests niosomes to be multilamellar vesicles with smooth surface. In-vitro diffusion study demonstrated that the drug diffused from optimized batch (F1) niosomal gel was found 95.69%. Optimized formulations were subjected for stability studies carried out at 4.0ºC ± 0.5 ºC and 28 ± 0.5ºC for 28 days. There was no important variation found in physical appearance, average particle size and % drug content of niosomes gel.

Stable Ethosome-like Catanionic Vesicles for Transdermal Hydrophilic Drug Delivery with Predictable Encapsulation Efficiency.

Lipid-like pseudo-double-chained catanionic surfactants have emerged as the attractive materials to prepare potential vesicular carriers in drug and gene delivery applications. In particular, the semi-spontaneous process has been developed to fabricate ethosome-like catanionic vesicles for the transdermal drug delivery. In this work, Arbutin (a water-soluble drug) encapsulation efficiency of ethosome-like catanionic vesicles fabricated from decyltrimethylammonium-tetradecylsulfate (DeTMA-TS, CH3(CH2)9 N(CH3)3-CH3(CH2)13SO4) and decyltrimethylammonium-dodecylsulfate (DeTMA-DS, CH3(CH2)9N(CH3)3-CH3(CH2)11SO4) with various amounts of ethanol and cholesterol in tris buffer solution was experimentally determined. A simple unilamellar vesicle (ULV) model, resulting in the theoretical encapsulation efficiency within ±10% error for most vesicle compositions, was also developed. Such agreement indirectly confirmed the formation of unilamellar vesicles by the preparation method. Stable ethosome-like catanionic vesicles by using catanionic surfactants with the aid of suitable amounts of ethanol and cholesterol, which led to polydispersity index (PDI) values of vesicle size distribution less than 0.3, were successfully prepared and their hydrophilic drug encapsulation efficiencies can be accurately predicted. Furthermore, the linear correlations of the trap volume ratio with both vesicle size and concentration of the extra added CHOL also provide important guidelines for controlling the drug loading of ethosome-like catanionic vesicles. The accomplishments reached for the novel vesicles are useful for developing their transdermal drug delivery applications.

Transfersomes- a Novel Vesicular Carrier for Enhanced Transdermal Delivery of Stavudine: Development, Characterization and Performance Evaluation

The aim of the present study was to investigate the potential of transfersomal formulations for transdermal delivery of Stavudine and to evaluate Span 80, Tween 80, Sodium cholate and Sodium deoxycholate as edge activators. Vesicles containing phosphatidylcholine (PC) mixed with edge activators and Stavudine were prepared by conventional rotary evaporation method and characterized by various parameters (vesicles shape and surface morphology, size and size distribution, entrapment efficiency, elasticity, turbidity and in vitro drug release). The compositions of refined formulations were predicted, liposomes prepared and tested against control. Skin permeation profile of transfersomal formulation bearing Stavudine was observed and the investigations revealed an enhanced transdermal flux (8.91±0.9 μg/cm2/hr) and decrease lag time (0.9 hr) for Stavudine. The obtained flux was nearly 7.5 and 12.04 times higher than conventional liposomal formulation bearing Stavudine and plain drug solution. These results suggested that transfersomes are potential vehicles for improved transdermal delivery of Stavudine and Span 80, Tween 80 and Sodium cholate were equivalent to Sodium deoxycholate as edge-activators.

Quality by Design Approach For Formulation Optimization of Ethosomal Vesicular Carrier of Curcumin

Quality by Design Approach For Formulation Optimization of Ethosomal Vesicular Carrier of Curcumin

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.

Emerging Technologies to Target Drug Delivery to the Skin - the Role of Crystals and Carrier-Based Systems in the Case Study of Dapsone.

Dapsone (DAP) is a long-established molecule that remains a promising therapeutic agent for various diseases mainly because it combines antimicrobial and anti-inflammatory activities. Its oral application, however, is limited by the dose-dependent hematological side effects that may rise from systemic exposure. As an alternative to overcome this limitation, the administration of DAP to the skin has witnessed prominent interest in the past 20years, particularly when applied to the treatment of dermatological disorders. In this review, all technological strategies proposed to the topical delivery of DAP are presented. Most of the reported studies have been devoted to the clinical use and safety of a gel formulation containing both solubilized and microcrystalline drug, however, the technological characteristics of such preparation are still missing. In parallel, the incorporation of DAP into vesicular and particulate carriers (e.g. nano- and microemulsions, niosomes, invasomes, bilosomes, cubosomes, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanocapsules and polymer-lipid-polymer hybrid nanoparticles) appears to be an alternative to provide greater drug release control, enhanced drug solubilization and follicular targeting. Indeed, the main application of DAP topical formulations reported in the literature was the treatment of acne vulgaris, a disease located in the hair follicle. Other diseases affecting different regions of the skin (e.g. cutaneous lupus erythematosus and cutaneous leishmaniasis), however, may also benefit from a topical therapeutic regimen containing DAP. Therefore, the investigation of appendageal route in comparison to passive transmembrane diffusion as a function of targeted disease, as well as pharmacokinetic studies, are perspectives highlighted herein. Such studies may drive future efforts towards the rational development of safe and effective technologies to deliver DAP to the skin. Graphical abstract.

Soft Malleable Vesicles: versatile carriers for efficient topical delivery of fungal therapeutics.

Fungal infections have become a subject of great concern and the incidence of fungal infections is increasing, presenting an enormous challenge to healthcare professionals. Since most of the fungal infections are occurring over the skin, the treatment option of these infections always involves topical application. However, in topical delivery drug reaches into systemic circulation through different barriers of skin. Nevertheless, due to the low permeability, skin restricts the movement of many drugs. Hence, a delivery system is required, which deliver the medicament into the skin layers or through the skin and into the systemic circulation. Ethosomes or Soft malleable vesicles are the novel lipid vesicular carrier that offer improved skin permeability and efficient delivery due to their structure and composition. They contain high concentration of ethanol, which increases the fluidity of the skin. Therefore, in the present paper, we have explored the utility of ethosomal systems in the topical treatment of fungal infections. Structure, compositions types, mechanism and techniques of preparation of ethosome also discussed in the paper.

The Challenge of Nanovesicles for Selective Topical Delivery for Acne Treatment: Enhancing Absorption Whilst Avoiding Toxicity.

Acne is a common skin disease that affect over 80% of adolescents. It is characterized by inflammation of the hair bulb and the attached sebaceous gland. To date, many strategies have been used to treat acne as a function of the disease severity. However, common treatments for acne seem to show several side effects, from local irritation to more serious collateral effects. The use of topical vesicular carriers able to deliver active compounds is currently considered as an excellent approach in the treatment of different skin diseases. Many results in the literature have proven that drug delivery systems are useful in overcoming the toxicity induced by common drug therapies, while maintaining their therapeutic efficacy. Starting from these assumptions, the authors reviewed drug delivery systems already realized for the topical treatment of acne, with a focus on their limitations and advantages over conventional treatment strategies. Although their exact mechanism of permeation is not often completely clear, deformable vesicles seem to be the best solution for obtaining a specific delivery of drugs into the deeper skin layers, with consequent increased local action and minimized collateral effects.

Development of curcumin-loaded composite phospholipid ethosomes for enhanced skin permeability and vesicle stability.

Ethosomes are widely applied as the carriers for the transdermal delivery of hydrophobic and hydrophilic drugs. Herein, curcumin-loaded ethosomes (CE) with different phospholipid composition were formulated and thoroughly compared. A significant interaction between the unsaturated phosphatidylcholine (PC) and saturated hydrogenated phosphatidylcholine (HPC) was found by molecular simulation and differential scanning calorimetry (DSC), which led to the reduction of PC peroxidation with the presence of HPC. Subsequently, the composite phospholipid ethosomes containing curcumin were prepared for the first time to evaluate their properties in comparison with the conventional ethosomes composed of PC (CE-P) or HPC (CE-H). CE with PC/HPC ratio of 1:1 (CE-P1H1) with the best vesicle stability and flexibility significantly decreased the uptake by HaCaT cells compared to CE-H and free curcumin, indicating reduced skin cell toxicity. Compared with free curcumin, CE-P1H1 had the highest transdermal efficiency (p<0.001), followed by CE-P (p<0.05), partly due to the fact that CE-P1H1 could disturb lipid domain of stratum corneum (SC). Moreover, CE-P1H1 was found to promote curcumin for deep penetration of the skin via the hair follicles route. Our study has shown that using composite phospholipid ethosomes as lipid vesicular carriers could enhance transdermal penetration of drugs and increase in the vesicle stability.

A COMPARATIVE ASSESSMENT OF VESICULAR FORMULATIONS: TRANSFERSOMES AND CONVENTIONAL LIPOSOMES LOADED IVABRADINE HYDROCHLORIDE

Objective: Ivabradine hydrochloride (IH), a benzazepine derivative used to treat cardiovascular disease angina pectoris. In this study IH-loaded novel carrier systems transfersomes (TFs) and conventional liposomes (CLs) were developed and compared for their efficacy to enhance the stability of drugs from degradation.&#x0D; Methods: TFs formulations (TF-1, TF-2 and TF-3) were prepared by using different biocompatible surfactants; tween-80 (TW), span-80(S) and sodium deoxycholate (SC) in the concentration ratio of 15 parts with 85 parts of soy phosphatidylcholine as phospholipid by thin-film hydration method. These vesicles were compared with CLs formulation (L-1) prepared in 7:3 molar ratio of soy phosphatidylcholine: cholesterol by following the same method. These vesicles were compared for physical appearance, vesicle shape, and size, percentage drug entrapment efficiency (%DEE), deformability index (DI), in vitro percentage cumulative drug release study, and physical stability studies. The chosen optimized novel carriers were observed under scanning electron microscopy.&#x0D; Results: The compared data demonstrated that the physical appearance for all vesicles was turbid and had a spherical shape. The size distribution was in the range of 129.0 nm to 273.5 nm in vesicles. The %DEE (79.0±0.94) and DI (35.0±1.9) was found maximum in TF-1 formulation that was 2.3 times higher than L-1 formulation. The in vitro percentage cumulative drug release study followed second-order polynomial kinetics that was 2.0 times higher than L-1and 2.9 times higher than the plain drug in 30 min (90.4±0.06%) from TF-1. The vesicles were found to be stable at refrigeration conditions.&#x0D; Conclusion: Thus, amongst of all vesicles TW loaded TFs (TF-1) was chosen as an excellent novel vesicular carrier for hydrophilic drugs due to its higher deformability behavior than CLs that protects the certain drugs from biodegradation and provides stability.

Liposomes as Anticancer Therapeutic Drug Carrier’s Systems: More than a Tour de Force

A liposome is a spherical vesicle composed of a bilayer of lipid with central aqueous cavity. Liposomes are the first nano vesicular drug delivery carriers, which are successfully translated into real-time clinical application and gained great potential in the past 30 years. The characteristics of liposomes to encapsulate both hydrophilic and hydrophobic drugs, their biocompatibility and biodegradability make it attractive nanocarriers in drug delivery area. Apart from this, great technical advancement has been made to develops second-generation liposomes named as stealth liposomes, cationic liposomes, triggered release liposomes and ligand targeted liposomes. This led to widespread use of liposomes in various areas including anticancer therapeutics, diagnostics and imaging agents. Therefore, the presents review article made an extensive discussion of various liposomes and its applications in cancer treatment.

Targeting Cancer using Curcumin Encapsulated Vesicular Drug Delivery Systems.

Curcumin is a major curcuminoid present in turmeric. The compound is attributed to various therapeutic properties, which include anti-oxidant, anti-inflammatory, anti-bacterial, anti-malarial, and neuroprotection. Due to its therapeutic potential, curcumin has been employed for centuries in treating different ailments. Curcumin has been investigated lately as a novel therapeutic agent in the treatment of cancer. However, the mechanisms by which curcumin exerts its cytotoxic effects on malignant cells are still not fully understood. One of the main limiting factors in the clinical use of curcumin is its poor bioavailability and rapid elimination. Advancements in drug delivery systems such as nanoparticle-based vesicular drug delivery platforms have improved several parameters, namely, drug bioavailability, solubility, stability, and controlled release properties. The use of curcumin-encapsulated niosomes to improve the physical and pharmacokinetic properties of curcumin is one such approach. This review provides an up-to-date summary of nanoparticle-based vesicular drug carriers and their therapeutic applications. Specifically, we focus on niosomes as novel drug delivery formulations and their potential in improving the delivery of challenging small molecules, including curcumin. Overall, the applications of such carriers will provide a new direction for novel pharmaceutical drug delivery, as well as for biotechnology, nutraceutical, and functional food industries.

First person – Laura Westrate

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Laura Westrate is first author on ‘Vesicular and uncoated Rab1-dependent cargo carriers facilitate ER to Golgi transport’, published in JCS. Laura conducted the research described in this article while a post-doctoral fellow in Dr Gia Voeltz's lab at University of Colorado Boulder, CO, USA. She is now an Assistant Professor at Calvin University, Grand Rapids, MI, USA, investigating the mechanisms behind protein transport and sorting in the endoplasmic reticulum.

Phospholipid Vesicles for Dermal/Transdermal and Nasal Administration of Active Molecules: The Effect of Surfactants and Alcohols on the Fluidity of Their Lipid Bilayers and Penetration Enhancement Properties.

This is a comprehensive review on the use of phospholipid nanovesicles for dermal/transdermal and nasal drug administration. Phospholipid-based vesicular carriers have been widely investigated for enhanced drug delivery via dermal/transdermal routes. Classic phospholipid vesicles, liposomes, do not penetrate the deep layers of the skin, but remain confined to the upper stratum corneum. The literature describes several approaches with the aim of altering the properties of these vesicles to improve their penetration properties. Transfersomes and ethosomes are the most investigated penetration-enhancing phospholipid nanovesicles, obtained by the incorporation of surfactant edge activators and high concentrations of ethanol, respectively. These two types of vesicles differ in terms of their structure, characteristics, mechanism of action and mode of application on the skin. Edge activators contribute to the deformability and elasticity of transfersomes, enabling them to penetrate through pores much smaller than their own size. The ethanol high concentration in ethosomes generates a soft vesicle by fluidizing the phospholipid bilayers, allowing the vesicle to penetrate deeper into the skin. Glycerosomes and transethosomes, phospholipid vesicles containing glycerol or a mixture of ethanol and edge activators, respectively, are also covered. This review discusses the effects of edge activators, ethanol and glycerol on the phospholipid vesicle, emphasizing the differences between a soft and an elastic nanovesicle, and presents their different preparation methods. To date, these differences have not been comparatively discussed. The review presents a large number of active molecules incorporated in these carriers and investigated in vitro, in vivo or in clinical human tests.

The Scope and Challenges of Vesicular Carrier-Mediated Delivery of Docetaxel for the Management of Cancer.

Since the discovery of liposomes, these vesicular carriers have attracted the researchers from all the vistas of the biomedical domain to explore and harness the potential benefits. Many novel drug delivery-based products have been approved by the United States Food and Drug Administration (USFDA) and other federal agencies of the globe, out of which the major share is of the liposomes and related carriers. Taking cognizance of it, the US-FDA has recently come up with 'Guidance for Industry on Liposome Drug Products'. In cancer management, chemotherapy is the most frequently employed approach which is still not devoid of untoward challenges and side effects. In chemotherapy, the taxanes, esp. Docetaxel shares a huge percentage in the prescription pattern. Also, the first marketed liposomal product was encasing one drug of this category. Henceforth, the present review will highlight the advances in the delivery of taxanes, in particular docetaxel, with an emphasis on the need, success and pharmacoeconomic aspects of such vesicular-carrier mediated docetaxel delivery.

Development and Characterization of Liposomal formulation for ophthalmic delivery of Prednisolone Acetate

Liposomal vesicular drug carriers for ocular delivery have earned a wide potential nowadays. Prednisolone Acetate liposome as ocular drug carriers have been demonstrated to be a useful mode to ameliorate bioavailability and patient abidance. Liposome was prepared by lipid extruder method. Liposome were characterized for entrapment efficiency (EE %), vesicle size, surface morphology and in vitro drug release. An ex vivo corneal permeation study was performed to determine the level of drug in the external eye tissue of goat and an ocular irritation assessment was done by Hen’s Egg Test - Chorioallantoic Membrane (HET-CAM) method. The optimized formulation of liposome had shown acceptable viscosity (1.21 ± 0.03 cps), refractive index (1.47±0.001), osmolarity (303 ± 3 mOsm) and pH measurement (7.12 ± 0.09). Liposome as drug delivery carriers were evidenced to be a anticipating impendent to enhance corneal contact and penetration as well as retention time in the eye ensuing in a prolonged action and enhanced bioavailability. The results of stability study exhibited stable profile of developed liposomes.