Non-ionic Surfactant Vesicles Research Articles

Evaluation of minor groove binders (MGBs) as novel anti-mycobacterial agents and the effect of using non-ionic surfactant vesicles as a delivery system to improve their efficacy.

The slow development of major advances in drug discovery for the treatment of Mycobacterium tuberculosis (Mtb) infection suggests a compelling need for evaluation of more effective drug therapies against TB. New classes of drugs are constantly being evaluated for anti-mycobacterial activity with currently a very limited number of new drugs approved for TB treatment. Minor groove binders (MGBs) have previously revealed promising antimicrobial activity against various infectious agents; however, they have not yet been screened against Mtb. The mycobactericidal activity of 96 MGB compounds against Mtb was determined using an H37Rv-GFP microplate assay. MGB hits were screened for their intracellular mycobactericidal efficacy against the clinical Beijing Mtb strain HN878 in bone-marrow-derived macrophages using standard cfu counting. Cell viability was assessed by CellTiter-Blue assays. Selected MGBs were encapsulated into non-ionic surfactant vesicles (NIVs) for drug delivery system evaluation. H37Rv-GFP screening yielded a hit-list of seven compounds at an MIC99 of between 0.39 and 1.56 μM. MGB-362 and MGB-364 displayed intracellular mycobactericidal activity against Mtb HN878 at an MIC50 of 4.09 and 4.19 μM, respectively, whilst being non-toxic. Subsequent encapsulation into NIVs demonstrated a 1.6- and 2.1-fold increased intracellular mycobacterial activity, similar to that of rifampicin when compared with MGB-alone formulation. MGB anti-mycobacterial activities together with non-toxic properties indicate that MGB compounds constitute an important new class of drug/chemical entity, which holds promise in future anti-TB therapy. Furthermore, the ability of NIVs to better deliver entrapped MGB compounds to an intracellular Mtb infection suggests further preclinical evaluation is warranted.

Abstract 2185: Cross-disciplinary optimization of nano-drug delivery to ovarian carcinoma and glioma cells

Abstract This study reports on the quantitative analysis of the diffusion and localization of a targeted drug delivery system (DDS) consisting of fluorescent labeled 0.01 µM paclitaxel-BODIPY 564/570 encapsulated in non-ionic surfactant vesicles embedded in a thermosensitive cross-linked chitosan hydrogel. This is a multi-tiered DDS that allows for enhanced stability, sustained and controlled delivery of embedded drugs to tumor sites, and reduced toxicity. We showed that cancer cells of epithelial origin, such as human ovarian epithelial carcinoma OV2008 and highly migratory mouse glioma G-26, overexpress MUC1, a mucin surface antigen, which effectively enhances the specific targeting capacity of chitosan. Utilizing this DDS we found that OV2008 carcinoma cells had ~2 times higher fluorescence intensity level than normal ovarian epithelial IMCC3 cells with a statistical significance at 5 min and 24 h incubation times suggesting that this DDS had a higher affinity for tumor cells. Therefore, we hypothesized that there is a difference in PTX diffusion towards epithelial origin tumor cells when compared to normal cells in both distance/location and time. Diffusion and localization of fluorescent labeled PTX was evaluated in vitro using confocal microscopy. The fluorescence intensity captured on the images was quantified with ImageJ software in OV2008 carcinoma cells and compared to IMCC3 normal cells at time intervals 5 min, 1 h, 24 h, 48 h, and 72 h. The fluorescence intensity image data was analyzed in multiple radial line segments separated into three different zones of 24 µm each to represent multiple diffusion distances. Our results showed that fluorescence intensity levels in the zones around the IMCC3 normal cells at 5 min and 1 h were significantly higher (p<0.05) than around OV2008 carcinoma cells correlating reciprocally with our finding of intracellular fluorescence intensity in these two cell lines. Therefore, the data evaluating fluorescence levels in the radial zones outside the cells indicated that the migrating DDS-PTX had already been taken up by the tumor cells. Furthermore, the normal cells which showed significantly lower intracellular levels of fluorescence had higher levels of fluorescence in the measured radial zones outside the cells. This PTX-BODIPY 564/570 diffusion data from in vitro studies is currently being used for computational modeling in the in vivo intracerebral model of G-26 glioma. It will be integrated with mathematical model simulations that describe the pharmacokinetic and pharmacodynamic (PK/PD) properties of this drug delivery system for the evaluation of its efficacy and to optimize drug delivery in vivo. Computational modelling is being done in Matlab using the treatment scenario of the post-surgical late-stage glioma. The simulation studies will be used to determine optimal drug concentrations, chitosan density, and localization. Citation Format: Rupin Singh, Rana Falahat, Eva Williams, Joseph O. Johnson, Norma Alcantar, Aleksandra Karolak, Katarzyna Rejniak, Marzenna Wiranowska. Cross-disciplinary optimization of nano-drug delivery to ovarian carcinoma and glioma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2185. doi:10.1158/1538-7445.AM2017-2185

Niosomes: An Update

Over decades researchers are striving to use the drugs in an efficient manner to treat various diseases. The efficient use can be explained as reduced dose, reduced side effects, reduced dosage frequency, greater patient compliance and maximum concentration of the drug at the site of action so as to reduce the undue exposure to the entire body. The article focuses on various advantages of vesicular systems (niosomes) to develop the effective delivery system to achieve maximum effective concentration. Niosomes, nonionic surfactant vesicles with lamellar structure which may be unilamellar and multilamellar serve to be efficient in providing these required advantages. The bilayer structure of niosomes being amphiphillic in nature can be used to deliver hydrophilic drugs in its aqueous core and lipophilic drugs in the bilayer made up of surfactants. Various additives in niosomes include nonionic surfactant as film forming agent, cholesterol as stabilizing and rigidizing agent for the bilayer and various charge inducers which develop a charge on the surface of niosomes and stabilize the prepared formulation by the resulting repulsive forces. This article also comprises of various breakthroughs in niosomal delivery of drugs representing various classes. On the basis of above information, the niosomes have been thoroughly exploited for the drug delivery system and still offer scope for research on various drugs for their maximum therapeutic utilization in management and treatment of various dreadful diseases.

Formulation of Nonionic Surfactant Vesicles (NISV) Prepared by Microfluidics for Therapeutic Delivery of siRNA into Cancer Cells.

Small interfering RNAs (siRNA) have a broad potential as therapeutic agents to reversibly silence any target gene of interest. The clinical application of siRNA requires the use of safe and effective delivery systems. In this study, we investigated the use of nonionic surfactant vesicles (NISV) for the delivery of siRNA. Different types of NISV formulations were synthesized by microfluidic mixing and then evaluated for their physiochemical properties and cytotoxicity. The ability of the NISV to carry and transfect siRNA targeting green fluorescent protein (GFP) into A549 that stably express GFP (copGFP-A549) was evaluated. Flow cytometry and Western blotting were used to study the GFP expression knockdown, and significant knockdown was observed as a result of siRNA delivery to the cells by NISV. This occurred in particular when using Tween 85, which was able to achieve more than 70% GFP knockdown. NISV were thus demonstrated to provide a promising and effective platform for therapeutic delivery of siRNA.

Comparison of the physical characteristics of monodisperse non-ionic surfactant vesicles (NISV) prepared using different manufacturing methods

Non-ionic surfactant vesicles (NISV) are synthetic membrane vesicles formed by self-assembly of a non-ionic surfactant, often in a mixture with cholesterol and a charged chemical species. Different methods can be used to manufacture NISV, with the majority of these requiring bulk mixing of two phases. This mixing process is time-consuming and leads to the preparation of large and highly dispersed vesicles, which affects the consistency of the final product and could hinder subsequent regulatory approval. In this study, we have compared the physical characteristics of NISV prepared using two conventional methods (thin-film hydration method and heating method) with a recently introduced microfluidic method. The resulting particles from these methods were assessed for their physical characteristics and in vitro cytotoxicity. Through microfluidics, nano-sized NISV were prepared in seconds, through rapid and controlled mixing of two miscible phases (lipids dissolved in alcohol and an aqueous medium) in a microchannel, without the need of a size reduction step, as required for the conventional methods. Stability studies over two months showed the particles were stable regardless of the method of preparation and there were no differences in terms of EC50 on A375 and A2780 cell lines. However, this work demonstrates the flexibility and ease of applying lab-on-chip microfluidics for the preparation of NISV that could be used to significantly improve formulation research and development, by enabling the rapid manufacture of a consistent end-product, under controlled conditions.

PH-sensitive niosomes: Effects on cytotoxicity and on inflammation and pain in murine models

pH-sensitive nonionic surfactant vesicles (niosomes) by polysorbate-20 (Tween-20) or polysorbate-20 derivatized by glycine (added as pH sensitive agent), were developed to deliver Ibuprofen (IBU) and Lidocaine (LID). For the physical-chemical characterization of vesicles (mean size, size distribution, zeta potential, vesicle morphology, bilayer properties and stability) dynamic light scattering (DLS), small angle X-ray scattering and fluorescence studies were performed. Potential cytotoxicity was evaluated on immortalized human keratinocyte cells (HaCaT) and on immortalized mouse fibroblasts Balb/3T3. In vivo antinociceptive activity (formalin test) and anti-inflammatory activity tests (paw edema induced by zymosan) in murine models were performed on drug-loaded niosomes. pH-sensitive niosomes were stable in the presence of 0 and 10% fetal bovine serum, non-cytotoxic and able to modify IBU or LID pharmacological activity in vivo. The synthesis of stimuli responsive surfactant, as an alternative to add pH-sensitive molecules to niosomes, could represent a promising delivery strategy for anesthetic and anti-inflammatory drugs.

The effects of hydration media on the characteristics of non-ionic surfactant vesicles (NISV) prepared by microfluidics

Non-ionic surfactant vesicles (NISV) are colloidal particles that provide a useful delivery system for drugs and vaccines. One of the methods that is used for NISV preparation is microfluidics in which the lipid components dissolved in organic phase are mixed with an aqueous medium to prepare the particles through self-assembly of the lipids. In this work, we examined the effect of using different types of aqueous media on the characteristics of the NISV prepared by microfluidics. Five aqueous media were tested: phosphate buffered saline, HEPES buffer, Tris buffer, normal saline and distilled water. The resulting particles were tested for their physical characteristics and cytotoxicity. The aqueous media were found to have significant effects on the physical characteristics of the particles, as well as their overall stability under different conditions and their cytotoxicity to different human cell lines. Careful consideration should be taken when choosing the aqueous media for preparing NISV through microfluidics. This is an important factor that will also have implications with respect to the entrapped material, but which in addition may help to design vesicles for different uses based on changing the preparation medium.

Development of a biocompatible creatinine-based niosomal delivery system for enhanced oral bioavailability of clarithromycin

Context: Nonionic surfactant vesicles have gained increasing scientific attention for hydrophobic drugs delivery due to their biocompatibility, stability and low cost.Objective: The aim of the present study was to synthesize and evaluate a novel creatinine-based nonionic surfactant in terms of its ability to generate biocompatible niosomal system for the delivery of Clarithromycin.Materials and Methods: The surfactant was synthesized by reacting creatinine with lauroyl chloride followed by characterization using 1HNMR and MS. The drug-loaded niosomal vesicles of the surfactant were characterized for drug encapsulation efficiency (EE) using LC-MS, vesicle size using dynamic light scattering (DLS) and vesicle shape using atomic force microscopy (AFM). The surfactant was also investigated for blood hemolysis, in vitro cytotoxicity against different cell lines and in vivo acute toxicity in mice. Furthermore, the in vivo bioavailability of Clarithromycin encapsulated in the novel niosomal formulation was investigated using rabbits and quantified through validated LC-MS/MS method.Results and discussion: Findings showed that vesicles were able to entrap up to 67.82 ± 1.27% of the drug, and were rounded in shape with a size around 202.73 ± 5.30 nm and low polydispersity. The surfactant caused negligible blood hemolysis, very low cytotoxicity and was found to be safe up to 2500 mg/kg body weight using mice. The niosomal formulation showed twofold enhanced oral bioavailability of Clarithromycin as compared to commercial formulations of the drug.Conclusion: The study has shown that the creatinine-based niosomes developed in our laboratory were biocompatible, safe and increased the oral bioavailability of the model hydrophobic Clarithromycin using experimental animals.

Fluconazole-loaded niosomal gels as a topical ocular drug delivery system for corneal fungal infections

Non-ionic surfactant vesicles containing fluconazole (FLZ) were prepared using, span 60 or span 80 and cholesterol in weight ratios of 1:1, 2:1 and 1:2. The prepared vesicles were characterized for size, entrapment efficiency, and in vitro drug release. The drug encapsulation efficiencies varied from 40.0% to 84.35%. The particle size ranged from 140 to 280 nm. Higher encapsulation was obtained by the span 60: cholesterol ratio of 2:1, which showed the best drug release. The selected niosomal formulations were incorporated into poloxamer 407 and chitosan gel formulations. Drug release from niosomal dispersions and niosomal gels, permeation of drug from niosomal gels through goat cornea and its antifungal activity were evaluated. Results showed that the surfactant: cholesterol ratio had a significant effect on the encapsulation efficiency and the size of vesicles. The niosomes prepared with 2:1 surfactant: cholesterol showed superior release over the other niosomal formulations. The drug release and permeation from poloxamer gel were higher than that from chitosan gel. Permeation study showed that, the flux of drug was dependent on the viscosity of the gel. The selected niosomal gels had excellent antifungal activity where the poloxamer niosomal gel was more effective compared to chitosan niosomal gel.

Development and optimization of boswellic acid-loaded proniosomal gel

Context: Boswellic acids (BAs) are isolated from oleo gum of Boswellia serrata and are mainly used as potential anti-inflammatory, hypolipidemic, immunomodulatory, and antitumor agents. Pharmacokinetic investigations of BAs uncover its poor bioavailability through digestive system thus creates a need for improved therapeutic responses which can possibly be achieved by developing formulations through novel delivery system.Objective: Present study was conducted to design topical BA-loaded proniosomal gel for the management of inflammatory disorders with enhanced bioavailability.Materials and methods: Nonionic surfactant vesicles were prepared using the coacervation phase separation method. A central composite design was employed to statistically optimize formulation variables using Design-Expert software. Three independent variables were evaluated: amount of surfactant (X1), amount of soya lecithin (X2), and amount of cholesterol (X3). The encapsulation efficiency percentage (Y1) and particle size (Y2) were selected as dependent variables.Results and discussion: The optimum formulation (F10) displayed spherical bi-layered vesicles under transmission electron microscopy with optimum particle size of 707.9 nm and high entrapment efficiency as 98.52%. In vitro skin permeation study demonstrated the most sustained release of 84.83 ± 0.153 mg/cm2 in 24 h. Anti-inflammatory activity of the gel showed a significant (p < 0.001) higher percentage inhibition as compared to the marketed gel at the same dose.Conclusion: The present study exhibited that BA-loaded proniosomal gel was better in terms of absorption, bioavailability, and release kinetics.

Molecular structure and dynamical properties of niosome bilayers with and without cholesterol incorporation: A molecular dynamics simulation study

Niosomes are non-ionic surfactant vesicles having a bilayer structure formed by self-assembly of hydrated surfactants, usually with cholesterol incorporation. Stability and mechanical properties of niosomes strongly depend on type of non-ionic surfactants and compositions used. In this study we present the structural and dynamical properties of niosome bilayers composed of sorbitan monostearate (Span60) with 0% and 50% cholesterol compositions which are investigated by using molecular dynamics simulations. The simulations reveal that niosome bilayer without cholesterol prefer to form in the gel phase with a higher order structure, while in the presence of cholesterol the bilayer exhibits more fluidity having a less ordered structure. The niosome bilayer with 50% cholesterol inclusion shows an increase of area per lipid (∼11%) and thickness (∼39%) compared with the niosome bilayer without cholesterol. The Span60 tailgroup orientation of the niosome bilayers without cholesterol exhibits more tilt (34.5o±0.5) than that of the bilayer with 50% cholesterol (15.4o±0.8). Additionally, our results show that the addition of cholesterol to the bilayer causes the higher in lateral and transverse diffusion, as well as an increase in the hydrogen bond number between Span60 and water. Such characteristics not only enhance the niosome stability but also increase the fluidity, which are necessary for the niosomal drug delivery.

Effect of different types of surfactants on the physical properties and stability of carvedilol nano-niosomes.

Background:Niosomes are non-ionic surfactant vesicles used as drug carriers for encapsulating both hydrophobic and hydrophilic drugs. The aim of this study is to evaluate the effect of different surfactants on the physical properties and stability of carvedilol niosomes designed to improve oral bioavailability.Materials and Methods:Different niosomal formulations were prepared using a film hydration method, with various mixtures of different non-ionic surfactants including Span 20, 40, and 60, and also Tween 20, 40, and 60, along with cholesterol. The physicochemical characteristics of the formulations were evaluated in vitro.Results:The drug encapsulation efficiency was reduced by using lauryl (C12) chain containing surfactants, that is, Span/Tween. Cholesterol content and drug entrapment were the main factors affecting the mean particle size of the niosomes. The drug release profiles from most of the formulations were fitted well with the Baker-Lonsdale model, indicating a diffusion-based drug release mechanism. Niosomes prepared from 50 and 40% of the cholesterol with 25 or 30% of Span/Tween 60 showed the highest stability due to their high transition temperature and solid state feature of these surfactants.Conclusions:From the results obtained, it may be concluded that nanoniosomes are promising stable carriers for the oral delivery of carvedilol.

Preparation of Nonionic Vesicles Using the Supercritical Carbon Dioxide Reverse Phase Evaporation Method and Analysis of Their Solution Properties.

We have previously reported a new preparation method for liposomes using supercritical carbon dioxide (scCO2) as a solvent, referred to as the supercritical carbon dioxide reverse phase evaporation (scRPE) method. In our previous work, addition of ethanol to scCO2 as a co-solvent was needed, because lipid molecules had to be dissolved in scCO2 to form liposomes. In this new study, niosomes (nonionic surfactant vesicles) were prepared from various nonionic surfactants using the scRPE method. Among the nonionic surfactants tested were polyoxyethylene (6) stearylether (C18EO6), polyoxyethylene (5) phytosterolether (BPS-5), polyoxyethylene (6) sorbitan stearylester (TS-106V), and polyoxyethylene (4) sorbitan stearylester (Tween 61). All these surfactants have hydrophilic-lipophilic balance values (HLBs) around 9.5 to 9.9, and they can all form niosomes using the scRPE method even in the absence of ethanol. The high solubility of these surfactants in scCO2 was shown to be an important factor in yielding niosomes without ethanol addition. The niosomes prepared with the scRPE method had higher trapping efficiencies than those prepared using the conventional Bangham method, since the scRPE method gives a large number of unilamellar vesicles while the Bangham method gives multilamellar vesicles. Polyoxyethylene-type nonionic surfactants with HLB values from 9.5 to 9.9 were shown to be optimal for the preparation of niosomes with the scRPE method.

Nioplexes encapsulated in supramolecular hybrid biohydrogels as versatile delivery platforms for nucleic acids

Supramolecular hydrogels based on N-protected phenylalanine (Fmoc–Phe–OH) were used to encapsulate non-ionic surfactant vesicles (niosomes).

Novel synthesis of biologically active CdS nanoclusters in cell-mimicking vesicles

ABSTRACTStable cadmium sulphide (CdS) nanoclusters have been synthesised in non-ionic surfactant vesicles (niosomes). The nanocluster characteristics show strong dependence on the Cd2+ precursor concentration. At low precursor concentration, aggregates comprising fine nanocrystals of CdS with diameter 2–5 nm are formed. At high precursor concentrations, crystalline CdS nanoclusters (15–20 nm in diameter) are formed. Interestingly, these nanoclusters reside exclusively in the vesicular bilayer. Moreover, these nanoclusters are highly photoluminescent and exhibit cytotoxicity towards cancerous HeLa cells. As the vesicular bilayer mimics the cell membrane, the present work is extremely relevant to the use of the CdS nanoclusters for diagnostic and therapeutic purpose.

Niosomes as transdermal drug delivery system for celecoxib: in vitro and in vivo studies

Nonionic surfactant vesicles containing celecoxib (CXB) as an anti-inflammatory drug were prepared using, Span 60 or Span 40 and cholesterol in the ratios of 1:0, 1:1 and 1:2. Prepared vesicles were characterized for encapsulation efficiency, particle size and drug release. The drug encapsulation efficiencies varied from 60.55 to 80.35 %. The vesicle size ranged from 170 to 235 nm. The high encapsulation was achieved by the ratio 1:1 of span 60:cholesterol and this formula showed significant in vitro release of the drug (80 %) as compared to other forms (P < 0.05). Among niosomal gels investigated, poloxamer 407 niosomal gel showed significant drug release (72 % after 12 h) over the other forms (P < 0.05). The results also showed that the release of CXB from the niosomes and niosomal gels obeyed the Higuchi’s diffusion model. The anti-inflammatory activity of the drug from different niosomal gel formulations was also studied using Carrageenan-induced rat paw edema method. The results showed that there is significant anti-inflammatory activity (75.45 %) of the poloxamer niosomal gel on rat paw edema (P < 0.05).

Abstract 3677: Enhanced targeted delivery of paclitaxel to tumor cells of epithelial and neuroectodermal origin using chlorotoxin-chitosan nanodelivery system

Abstract We report a development of a novel localized nanodelivery system featuring an enhanced targeted and controlled paclitaxel (PTX) delivery to epithelial and neuroectodermal origin tumor cells. The presented drug delivery system consists of a chitosan hydrogel embedded with PTX loaded non-ionic surfactant vesicles (PTX-niosomes) and chlorotoxin (CTX). We found a higher accumulation of chitosan on the surface of ovarian epithelial carcinoma cells known to overexpress MUC1 antigen as compared to normal ovarian epithelial cells. We therefore hypothesized that besides serving as a localized drug delivery platform, chitosan hydrogel can actively target MUC1 overexpressing tumor cells. To further improve the tumor-specific delivery of PTX, we have incorporated CTX, a 36-amino acid peptide, which binds to tumor cells of neuroectodermal origin, but not to non-transformed cells. Using a High Performance Liquid Chromatography (HPLC) assay, we have measured the in-vitro release profiles of PTX from chitosan hydrogel embedded with PTX-niosomes and CTX. We have assessed the morphology of CTX and PTX-nisomes as well as chitosan hydrogel embedded with PTX-niosomes and CTX using Transmission Electron Microscopy (TEM). We have used Attenuated Total Reflectance-Fourier Transform Infra-Red (ATR-FTIR) spectroscopy to investigate the possible molecular interactions between chitosan hydrogel and various tumor cells. To better understand the mechanism involved in interactions between chitosan and specific tumor cells, we have developed a new Cell based Enzyme Linked Immunosorbent Assay (Cell ELISA) allowing us to quantify the expression level of MUC1 in epithelial and neuroectodermal origin tumor cells. Our Cell ELISA results revealed higher expression level of MUC1 (around 1.5 fold) in ovarian epithelial carcinoma cell line (OV2008) when compared to normal ovarian epithelial cell line (MCC3). The ATR-FTIR results showed a specific interaction of chitosan with OV2008 cells implying the mucoadhesive property of chitosan and its potential in targeting of MUC1 overexpressing tumor cells. We observed a sustained PTX release from chitosan hydrogel embedded with PTX-niosomes (&amp;lt; 40% of cumulative release occurred within two weeks). Release studies in cell-free system also indicated that embedding CTX along with the niosomes does not have any adverse effect on the controlled release of PTX from the chitosan network. In fact, attachment of CTX to the surface of PTX-niosomes shown by TEM imaging improves the stability of PTX-niosomes resulting in extended release rates. Together these findings indicate that the proposed drug delivery system with the distinctive tumor targeting features and extended release profiles would improve the specific delivery of PTX to epithelial and neuroectodermal origin tumor cells. Citation Format: Rana Falahat, Eva Williams, Marzenna Wiranowska, Ryan Toomey, Norma Alcantar. Enhanced targeted delivery of paclitaxel to tumor cells of epithelial and neuroectodermal origin using chlorotoxin-chitosan nanodelivery system. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3677. doi:10.1158/1538-7445.AM2015-3677

Formulation and Evaluation of Clotrimazole Niosomal Gel for Topical Application

Objective: In the present investigation, an attempt is made to develop and characterize niosomal gel formulation of clotrimazole to increase retention time in the dermis layer through controlled release of the drug. Methodology: Clotrimazole niosomes were prepared by thin film hydration method using span 40 (as non-ionic surfactant) and cholesterol (as stable vesicle forming agent). The niosomal dispersion was evaluated for vesicle size, surface morphology, percent entrapment efficiency and in vitro drug release. Results: Among the five formulations prepared, the formulation CN3 (containing 100 mg drug, 200 mg surfactant) was found to be promising. Selected niosomal suspension (CN3) containing clotrimazole equivalent to 2 % w/w was incorporated into gel base composed of carbopol (1%), triethanolamine 0.3% and distilled water quantity sufficient. The gel was studied for it’s different parameters such as pH, in vitro drug release, anti-fungal activity and skin irritation effect. Conclusion: The studies suggest that encapsulating clotrimazole in nonionic surfactant vesicles would provide better patient compliance by achieving prolonged release of the drug to the dermis with improved efficacy.

Novel method of niosome generation using supercritical carbon dioxide part I: process mechanics

A novel method for the production of non-ionic surfactant vesicles (niosomes) using an rapid expansion of supercritical solution (RESS)-based process coupled with a gas ejector is presented along with an investigation of parameters affecting niosome morphology, size and encapsulation efficiency of a 0.2 M d-glucose solution in Tris buffer at physiological pH. The solubility of the non-ionic surfactant polyoxyethylene(4) sorbitan monostearate in SC-CO2 was determined at three pressures (10, 15 and 20 MPa) and three temperatures (40, 50 and 60 °C). Mole fraction of Tween61 in the vapor phase increased with pressure at 40 °C, but did not change with pressure at 50 or 60 °C. Solubility data were correlated using the Peng–Robinson equation of state (PREOS) with the Panagiotopoulos and Reid mixing rule. Vesicles were either multilamellar or unilamellar, depending on the degree of precipitation of the lipid formulation at the point of aqueous cargo introduction. Vesicle particle size distributions were bimodal, with the 80–99% of the liposomal volume contributed niosomes ranging in size from 3 to 7 μm and the remaining niosomes ranging from 239 to 969 nm, depending on the system configuration. Encapsulation efficiency as high as 28% using the gas ejector to introduce the glucose cargo solution was achieved. Vesicle particle size and encapsulation efficiency were shown to be dependent on cargo droplet formation.

ROLE OF NIOSOMES AND PRONIOSOMES FOR ENHANCING BIOAVAILABILITY OF DRUGS

Niosome are non-ionic surfactant vesicles obtained on hydration of synthetic nonionic surfactants, with or without incorporation of cholesterol or their lipids. They are vesicular systems similar to liposomes that can be used as carriers of amphiphilic and lipophilic drugs. Noisome are promising vehicle for drug delivery and being non-ionic; and Niosomes are biodegradable, biocompatible nonimmunogenic and exhibit flexibility in their structural characterization. Niosomes can entrap both hydrophilic and lipophilic drugs and can prolong the circulation of the entrapped drug in body. Proniosomes are dry formulation of water soluble carrier particles that are coated with surfactant. They are rehydrated to form niosomal dispersion immediately before use on agitation in hot aqueous media within minutes. Proniosomes and niosomes are physically stable during the storage and transport. Drug encapsulated in the vesicular structure of proniosomes prolong the existence of drug in the systematic circulation and enhances the penetration into target tissue and reduce toxicity. From a technical point of view, niosomes and proniosomes are promising drug carriers as they possess greater chemical stability and lack of many disadvantages associated with liposomes, such as high- cost and variable purity problems of phospholipids. The present review emphasizes on overall methods of preparation characterization and applicability of niosomes and proniosomes in targeted drug delivery. KEYWORDS: proniosomes, targeted , Niosome,