Elastic Vesicles Research Articles

Development of transferosomes for topical ocular drug delivery of curcumin

BackgroundTransferosomes (TFS) are ultra-deformable elastic bilayer vesicles that have previously been used to enhance gradient driven penetration through the skin. This study aimed to evaluate the potential of TFS for topical ocular drug delivery and to compare their penetration enhancing properties in different ocular tissues. MethodsCurcumin-loaded TFS were prepared using Tween 80 as the edge activator. Drug release and precorneal retention of the TFS were evaluated in vitro, while their ocular biocompatibility and bioavailability were evaluated ex vivo using a curcumin solution in medium chain triglycerides as the oily control. ResultsThe TFS had a narrow size distribution with a particle size less than 150 nm and an entrapment efficiency greater than 99.96 %. Burst release from the TFS was minimal and the formulation showed good corneal biocompatibility. Moreover, enhanced corneal and conjunctival drug penetration with significantly greater and deeper drug delivery was observed with TFS. ConclusionTFS offer a promising platform for ocular delivery of hydrophobic drugs. This study, for the first time, elucidates the effect of tissue morphology and osmotic gradients on drug penetration in different ocular tissues.

Elastic vesicles for enhancing the transdermal delivery of Olmesartan Medoxomil

Elastic vesicles for enhancing the transdermal delivery of Olmesartan Medoxomil

Transferosome- A Noval Drug Delivery System

The skin's barrier function typically places restrictions on the transdermal administration of medications. One of the most contentious techniques for transdermal distribution of active ingredients is vesicular systems. After elastic vesicles such as transferosomes, ethosomes, cubosomes, phytosomes, etc. were discovered, there was a renewed interest in developing transdermal delivery systems. In order to provide active compounds transdermally, this paper describes the composition, penetration mechanisms, production processes, and characterization techniques of transferosomes. A medication must cross one or more biological membranes or barriers at different sites in order to be absorbed, distributed into organs and tissues, and removed from the body. Substance transport refers to the passage of a substance through a membrane in this manner. The medications must get through the membranous barrier in order to be absorbed by the body. In an effort to reduce the amount of medicine in the remaining tissues and concentrate the drug in the targeted tissues, several delivery systems were devised. As a result, the medication has no effect on the tissues nearby. Furthermore, medication loss does not occur. Furthermore, the localization of the drug prevents drug loss, resulting in the medication's optimum efficacy. As such, there is a lot of interest in phospholipid-based carrier systems nowadays.

Formulation optimization and PK/PD evaluation of novel valsartan bilosomes enhancing transdermal drug delivery

RationaleThe skins capillary network makes it the bodys most accessible organ. However, the topmost layer of skin, known as stratum corneum (SC), is a substantial diffusional barrier for most drugs. It is suggested that edge activators (EAs) may provide the lipid bilayer of innovative elastic vesicles with ultra-flexibility that can penetrate SC employing high self-optimising deformability. It is fact that the therapeutic activity of lipophillic drugs can be improvized by incorporating novel formulations into the colloidal system. Aim and objectThe primary objective of this research work focused to formulation and optimization of novel bilosomes containing valsartan (VLT). MethodsThin film hydration (TFH) technique developed bilosomes in a 33-factorial design. Valsartan bilosomes (VLT-B) and valsartan bilosomal gels (VLT-BG) efficacy was assessed using ex vivo, in vitro and in vivo investigations. ResultsVLTBG had a higher area under the curve (AUC) and plasma concentration (Cmax) in the tested animals than the VLT oral solution. The optimised VLTB had 136.48 ± 7.82 nm diameter, −48.37 ± 0.49 mV of surface charge, and 88.56 ± 1.73 % of drug encapsulation. Oral VLT solution and VLT bilosomal gel Cmax were 52.37 and 215.39 μg/mL at 2 and 16 h, respectively. The AUC(0–∞) with the oral and transdermal application of the VLTBG was found to be 0.430 μg h/mL and 67.21 μg h/mL, respectively. ConclusionThe outcomes supported the hypothesis that bilosomes enhance VLT flow and concluded that the skin is better than the drug solution.

Design and assessment of in silico screened diosmin incorporated ultra-flexible topical lipid gel system for the treatment of varicose vein

The ultra-flexible lipid gel system (UFLGS) consists of bilayer lipid membranes, responsible for highly elastic and deformable vesicles compared to conventional topical systems. Varicose veins are abnormal, dilated blood vessels resulting from weakening in the wall of the blood vessels. A flavonoid diosmin is highly potential to alleviate circulatory issues by altering blood veins’ elasticity and suppleness. Schrodinger 2023-1 suite device was used for molecular docking study. Ultra-flexible lipid nanosuspension (UFLNS) was developed and optimized. Then, they are characterized for Fourier transform infrared spectroscopy, differential scanning calorimetry, entrapment efficiency, transmission electron microscopy, atomic force microscopy, and turbidity measurement studies. After incorporating into the aqueous gelling agent Carbopol 934, Diosmin UFLGS (DUFLGS) was compared with the diosmin conventional gel system (DCGS) for its physicochemical properties. The docking score was –8.507, representing good interaction and binding affinity for nuclear factor-kappaB-inducing kinase. The particle size, polydispersity index, and surface charge of optimized diosmin-loaded UFLNS (DUFLNS) were found to be ideal values 144.56 ± 5.1 nm, 0.397 ± 0.13, and –24 ± 0.9 mV, respectively. The results of DUFLNS, DUFLGS, and DCGS showed skin retention values of 55.5% ± 13%, 83.44% ± 12%, and 66.39% ± 14%, respectively. The sustained release of the DUFLGS is owing to the elasticity of the ultra-flexible lipids, thereby the penetration enhanced compared to DCGS.

Exploiting response surface D-optimal design study for preparation and optimization of spanlastics loaded with miconazole nitrate as a model antifungal drug for topical application

PurposeSkin fungal infections are widely spreading worldwide and are considered a main cause of skin, mucous membranes, and systemic diseases. In an approach to enhance the topical delivery of miconazole nitrate (MZN) as a poorly permeable antifungal agent, spanlastics nanocarriers as a type of elastic vesicles were adopted in the current work.MethodsMZN spanlastics were prepared and optimized according to a D-optimal response surface design to investigate the influence of formulation variables, edge activator (EA) percentage, EA type on particle size (PS), and drug entrapment efficiency percentage (% EE) as dependent variables. The spanlastics optimized formula (F7) was further assessed for its elasticity and physico-pharmaceutical properties before being incorporated into a gel. The F7 gel formula was also examined for its physical properties, in vitro release, in vitro antifungal activity against Candida albicans (ATCC® 10231), and ex vivo skin deposition studies. The results of the F7 gel formula were compared to the F7 aqueous dispersion.ResultsThe D-optimal design revealed that F7, developed using Tween 60 as EA and Span 60 at a weight ratio 2:8, is the optimized formula. F7 was an elastic, spherical, non-aggregated vesicle with an average PS of 210 nm and a drug entrapment efficiency of 90%. The drug was present in an amorphous form within the vesicles. The gel form of F7 showed a prolonged drug release behavior relative to the solution form, where 75% of the drug was released over 10 h for the former and 5 h for the latter. The antifungal study revealed a significant (p < 0.05) increase in the zone of inhibition of Candida albicans (ATCC® 10231) demonstrated by spanlastics compared to MZN suspension at the same concentration level. MZN suspension showed cytotoxic activity at a concentration of 20 μg/mL and above; the incorporation of the drug in spanlastics dispersion or gel form increased the cell viability percentage. The skin deposition studies showed that F7 deposition in the dermal layer, where deep skin infections occur, is 164-folds that of the plain drug.ConclusionsThe results confirm the potential application of MZN-spanlastics to treat deeply seated skin fungal infections.

In vitro/In vivo Evaluation of Elastic Nano-lipid Carriers of Aztreonam for Pneumonic Lungs.

The liposomal inhalation of drugs has been extensively researched for the invasion of biofilms and macrophages in the infected lungs. The present study aimed to explore the in vitro and in vivo effects of elastic nano-lipid vesicles of aztreonam for pulmonary delivery. Elastic nano lipid vesicles of the drug were successfully prepared with the commonly abundant lung phospholipids (LIPOID S PC-3, LIPOID PC 16:0/16:0), cholesterol, and span 20. Four such formulations were evaluated for their physicochemical properties, in vitro diffusion, and cytotoxicity. The best formulation was subjected to stability, in vivo drug deposition on the pneumonic lungs, and histopathological studies. The characterization of the lipid vesicles in terms of particle size, zeta potential, and surface morphology confirmed the formation of stable nanolipid vesicles of the drug. The presence of surfactant in the lipid vesicles exhibited high bilayer stability, entrapment, and diffusion of the drug. The in vitro diffusion study revealed the biphasic characteristic with an initial burst, followed by sustenance for 8 h. A remarkable drug uptake was observed in the epithelial cell line of CHO Cricetulus griseus in the presence of surfactant. The drug was retained on the pneumonic lungs for 8 h. The histopathological study of lung tissue revealed that surfactant-based lipid vesicles could attenuate lung fibrosis significantly. It can be concluded that elastic nano lipid vesicular system of aztreonam could be a paradigm for targeting and localization of the drug with a long residence time in the lungs.

Formulasi Sistem Vesikel Elastik Surfaktan Nonionik Ekstrak Etanol Rimpang Etlingera alba dalam Sediaan Gel

Etlingera alba is a plant in Southeast Sulawesi that has antioxidant activity. Natural ingredients such as herbal medicine require a delivery system that facilitates them to reach the site of drug action, especially for transdermal delivery. The elastic vesicle system is a transdermal delivery system that can increase the penetration of active substances at the skin through the act of phospholipids on the skin's lipid bilayer and the deformability of the vesicles. This study aims to formulate and evaluate Etlingera alba rhizome ethanolic extract's elastic vesicle gel to obtain the optimal concentration of Tween 60 as a vesicle former and carbopol as a gel base. Preparation of elastic vesicles of Etlingera alba ethanolic extract using the heat method through variations Tween 60's concentration, namely 5%(F1); 10%(F2); 15%(F3); and 20%(F4). Meanwhile, elastic vesicle gel formulation of the ethanol extract of Etlingera alba rhizome used various concentrations of 0.5% carbopol gel base (FGel 1); 1% (FGel 2); 1.5% (FGel 3); and 2% (FGel 4). The results obtained were the optimum concentration of Tween 60 as a constituent of elastic vesicles of 15% (F4) with spherical morphology using an optical microscope, vesicle size of 10.45 nm, and polydispersity index of 0.280 using a Particle Size Analyzer. In addition, the optimal concentration of carbopol as a base for elastic vesicle gel is a concentration of 0.5% (GGel 1) with white color, distinctive aroma, and thick texture, and has a pH of 6, a viscosity of 2,366 cPs, spread of 6.8 cm, and physically stable through cycling test.

Topical Delivery of Elastic Liposomal Vesicles for Treatment of Middle and Inner Ear Diseases.

We present a topical drug delivery mechanism through the ear canal to the middle and inner ear using liposomal nanoparticles without disrupting the integrity of the tympanic membrane. The current delivery method provides a noninvasive and safer alternative to transtympanic membrane injections, ear tubes followed by ear drops administration, and systemic drug formulations. We investigate the capability of liposomal NPs, particularly transfersomes (TLipo), used as drug delivery vesicles to penetrate the tympanic membrane (TM) and round window membrane (RWM) with high affinity, specificity, and retention time. The TLipo is applied to the ear canal and found to pass through the tympanic membrane quickly in 3 h post drug administration. They are identified in the middle ear cavity 6 h and in the inner ear 24 h after drug administration. We performed cytotoxicity in vitro and ototoxicity in vivo studies. Cell viability shows no significant difference between the applied TLipo concentration and control. Furthermore, auditory brainstem response (ABR) reveals no hearing loss in 1 week and 1 month post-administration. Immunohistochemistry results demonstrate no evidence of hair cell loss in the cochlea at 1 month following TLipo administration. Together, the data suggested that TLipo can be used as a vehicle for topical drug delivery to the middle ear and inner ear.

Transethosomes: A Breakthrough System for Transdermal and Topical Drug Delivery

The major hindrance in transdermal delivery of drugs is complex barrier of stratum corneum. New generations lipid based nano-system, particularly transethosomes have ability to permeate from rigid network of stratum corneum. They have proved to be a promising tool for the transport of drugs. This article reviews these ethanol-based, elastic, and deformable vesicles. The major components that provide the vesicles their distinct properties are phospholipids, ethanol, edge activator, and water. Ethanol imparts softness and edge activator increases the permeation by providing elasticity, making it possible to deliver drug molecules in blood. It is a non-invasive technique that can be used as a carrier for NSAID, anticancer, antifungal, and antihypertensive, among other drugs.

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.

Two-dimensional hydrodynamics of a Janus particle vesicle

We develop a new model, to our knowledge, for the many-body hydrodynamics of amphiphilic Janus particles suspended in a viscous background flow. The Janus particles interact through a hydrophobic attraction potential that leads to self-assembly into bilayer structures. We adopt an efficient integral equation method for solving the screened Laplace equation for hydrophobic attraction and for solving the mobility problem for hydrodynamic interactions. The integral equation formulation accurately captures both interactions for near touched boundaries. Under a linear shear flow, we observe the tank-treading deformation in a two-dimensional vesicle made of Janus particles. The results yield measurements of intermonolayer friction, membrane permeability and, at large shear rates, membrane rupture. The simulation studies include a Janus particle vesicle in both linear and parabolic shear flows, and interactions between two Janus particle vesicles in shear and extensional flows. The hydrodynamics of the Janus particle vesicle is similar to the behaviour of an inextensible, elastic vesicle membrane with permeability.

Vesicle shape transformations driven by confined active filaments

In active matter systems, deformable boundaries provide a mechanism to organize internal active stresses. To study a minimal model of such a system, we perform particle-based simulations of an elastic vesicle containing a collection of polar active filaments. The interplay between the active stress organization due to interparticle interactions and that due to the deformability of the confinement leads to a variety of filament spatiotemporal organizations that have not been observed in bulk systems or under rigid confinement, including highly-aligned rings and caps. In turn, these filament assemblies drive dramatic and tunable transformations of the vesicle shape and its dynamics. We present simple scaling models that reveal the mechanisms underlying these emergent behaviors and yield design principles for engineering active materials with targeted shape dynamics.

Tuning cellular uptake of nanoparticles via ligand density: Contribution of configurational entropy

The bioactivity of nanoparticles (NPs) crucially depends on their ability to cross biological membranes. A fundamental understanding of cell-NP interaction is hence essential to improve the performance of the NP-based biomedical applications. Although extensive studies of cellular uptake have converged upon the idea that the uptake process is mainly regulated by the elastic deformation of the cell membrane or NP, recent experimental observations indicate the ligand density as another critical factor in modulating NP uptake into cells. In this study, we propose a theoretical model of the wrapping of an elastic vesicle NP by a finite lipid membrane to depict the relevant energetic and morphological evolutions during the wrapping process driven by forming receptor-ligand bonds. In this model, the deformations of the membrane and the vesicle NP are assumed to follow the continuum Canham-Helfrich framework, whereas the change of configurational entropy of receptors is described from statistical thermodynamics. Results show that the ligand density strongly affects the binding energy and configurational entropy of free receptors, thereby altering the morphology of the vesicle-membrane system in the steady wrapping state. For the wrapping process by the finite lipid membrane, we also find that there exists optimal ligand density for the maximum wrapping degree. These predictions are consistent with relevant experimental observations reported in the literature. We have further observed that there are transitions of various wrapping phases (no wrapping, partial wrapping, and full wrapping) in terms of ligand density, membrane tension, and molecular binding energy. In particular, the ligand and receptor shortage regimes for the small and high ligand density are, respectively, identified. These results may provide guidelines for the rational design of nanocarriers for drug delivery.

Implementing Spanlastics for Improving the Ocular Delivery of Clotrimazole: In vitro Characterization, Ex vivo Permeability, Microbiological Assessment and In vivo Safety Study.

PurposeThe aim of this study was to encapsulate clotrimazole (CLT), an antifungal drug with poor water solubility characteristics, into spanlastics (SPs) to provide a controlled ocular delivery of the drug.MethodsSpan 60 was used in the formulation of SPs with Tween 80, Pluronic F127, or Kolliphor RH40 as an edge activator (EA). The presence of EA offers more elasticity to the membrane of the vesicles which is expected to increase the corneal permeation of CLT. SPs were prepared using ethanol injection method applying 32 complete factorial design to study the effect of formulation variables (ratio of Span 60: EA (w/w) and type of EA) on SPs characteristics (encapsulation efficiency percent (EE%), average vesicle size (VS), polydispersity index (PDI) and zeta potential (ZP)). Design-Expert software was used to determine the optimum formulation for further investigations.ResultsThe optimum formulation determined was S1, which contains 20 mg of Tween 80 used as an EA and 80 mg of Span 60. S1 exhibited EE% = 66.54 ± 7.57%, VS = 206.20 ± 4.95 nm, PDI = 0.39 ± 0.00 and ZP = −29.60 ± 0.99 mV. S1 showed highly elastic sphere-shaped vesicles. Furthermore, S1 displayed a sustained release profile and a higher ex vivo permeation across rabbit cornea relative to CLT suspension. Also, S1 revealed superior inhibition of Candida albicans development compared to CLT suspension applying 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction technique. Moreover, in vivo histopathological examination assured the safety of S1 after ophthalmic application in mature male albino rabbits.ConclusionOverall, the outcomes revealed the marked efficacy of SPs for ocular delivery of CLT.

A NARRATIVE REVIEW ON TRANSFERSOMES: VESICULAR TRANSDERMAL DELIVERY SYSTEM FOR ENHANCED DRUG PERMEATION

Transdermal administration of drug is generally limited by the barrier function of the skin vascular system are one of the most controversial method for transdermal delivery of active substance. transdermal drug delivery system is designed to deliver biological active agents through the skin, principally by diffusion for local internal if not systemic effects. The transdermal delivery system was relaunched after the discovery of elastic vesicles like transfersome, ethosome, cubosome, phytosome etc. Transfersomes are a form of elastic or deformable vesicle, which were introduced in the early 1990s. Elasticity is generated by incorporation of edge activator in lipid bilayer structure. Drug absorbed and distributed into organs and tissue and eliminated from the body it must pass through one or more biological membranes at various locations such movement of drug across the membrane is called as drug transport for the drug delivery to cross the body it should pass through the membrane barrier. This concept of drug delivery system was designed in attempt to concentrate the amount of drug in the remaining drug; therefore, the phospholipid-based carrier system is of considerable interest in the era.

Stochastic phase field α-Navier-Stokes vesicle-fluid interaction model

We consider a stochastic perturbation of the phase field alpha-Navier-Stokes model with vesicle-fluid interaction. It consists in a system of nonlinear evolution partial differential equations modeling the fluid-structure interaction associated to the dynamics of an elastic vesicle immersed in a moving incompressible viscous fluid. This system of equations couples a phase-field equation -for the interface between the fluid and the vesicle- to the alpha-Navier-Stokes equation -for the viscous fluid- with an extra nonlinear interaction term, namely the bending energy. The stochastic perturbation is an additive space-time noise of trace class on each equation of the system. We prove the existence and uniqueness of solution in classical spaces of L2 functions with estimates of non-linear terms and bending energy. It is based on a priori estimate about the regularity of solutions of finite dimensional systems, and tightness of the approximated solution.

Investigating the Potential of Phosphatidylcholine-Based Nano-Sized Carriers in Boosting the Oto-Topical Delivery of Caroverine: in vitro Characterization, Stability Assessment and ex vivo Transport Studies.

PurposeDrug delivery into the inner ear across the intact tympanic membrane (TM) has been a challenge in the treatment of inner ear disorders. In this study, nano-sized carriers were formulated for improving the non- invasive oto-topical delivery of caroverine for the treatment of tinnitus.MethodsCaroverine was loaded into two types of phospholipid-containing systems, namely, nano elastic vesicles (EVs) and phosphatidylcholine-based liquid crystalline nano-particles (PC-LCNPs). The prepared formulations were characterized for their drug loading, particle size, polydispersity index, zeta potential, morphological features by transmission electron microscopy (TEM), and physicochemical stability. In addition, comparative ex vivo transport study was carried out using rabbits’ TM for both types of formulations.ResultsThe findings show a significant superiority of PC-LCNPs over the EVs formulations in the drug payload (1% and 0.25%, respectively), physical stability and the efficiency of permeation across rabbits’ TM. The results showed a more than twofold increase in the cumulative drug flux values of PC-LCNPs (699.58 ± 100 µg/cm2) compared to the EVs (250 ± 45 µg/cm2) across the TM.ConclusionThe current study revealed the smart physicochemical properties of PC-LCNPs demonstrating the potential of this carrier as a new attractive candidate for improving the non-invasive oto-topical delivery of caroverine.

Fabrication of novel topical drug loaded elastic membrane vesicles of liposomes as a tool for dermal delivery in effective treatment of psoriasis

Fabrication of novel topical drug loaded elastic membrane vesicles of liposomes as a tool for dermal delivery in effective treatment of psoriasis

A Comparative Formulation Development and Evaluation of Tazarotene Ethosomal and Transfersomal Gel for Effective Management of Acne

Acne vulgaris is the most prevalent disorder in the period before puberty when increased adrenal androgen level causes enlargement of the sebaceous glands and it increased the production of sebum on the face, chest, and back. This disease is caused due to interaction between many causative agents or pathogenic components which lead to formation of the acne and those are seborrhea, follicular hyper keratinization, microbial formation of pilosebaceous unit by Propionibacterium acne and arrival of inflammatory mediators. Tazarotene is a well-known retinoid related to vitamin A that belongs to an acetylenic class of retinoid, used in the management of acne. Oral administration of Tazarotene causes changes in bone morphology after prolonged exposure to high doses, which also exhibit teratogenicity but this does not occur with topical delivery. Ethosomes are non-invasive delivery carriers enabling drugs to reach to the bottom of the skin layers and/or the system and transfersomes are the self-adaptable ultra-deformable flexible elastic bilayer vesicles composed of phospholipids able to penetrate through the pores of skin even smaller than its size. Present research aims the comparative evaluation of ethosomal and transfersomal gels loaded with Tazarotene in the treatment of acne. In the present study, ethosomes and transfersomes were formulated by the cold method and hand-shaking method, respectively, followed by loading of Tazarotene and development into gel formulation. The formulated gel samples were evaluated for in vitro release study, in vitro permeation study, in vitro anti-acne study, in vivo percutaneous permeation study by CLSM, and in vivo anti-acne study. The results proved that both the formulated ethosomal and transfersomal gels have better permeation through the skin but ethosomal gel showed better release in comparison to transfersomal gel, also final gels exhibited the anti-acne potentiality.