Niosomal Vesicles Research Articles

Enhanced Permeation of Methotrexate via Loading into Ultra-permeable Niosomal Vesicles: Fabrication, Statistical Optimization, Ex Vivo Studies, and In Vivo Skin Deposition and Tolerability.

The aim of this study was to incorporate methotrexate (MTX) into ultra-permeable niosomal vesicles, containing cremophor RH40 as an edge activator (EA) and polyvinyl alcohol (PVA) as a stabilizer to enhance the drug permeation. Formulae were prepared by ethanol injection method following a Box-Behnken design in order to optimize the formulation variables (EA%, stabilizer %, and sonication time). To investigate the role of both cremophor RH40 and PVA, conventional MTX niosomes and MTX niosomes containing PVA only were fabricated. Drug entrapment efficiency percent (EE%), particle size (PS) analysis, zeta potential (ZP) measurements, and transmission electron microscopy (TEM) were conducted to characterize the vesicles. Cell viability studies and ex vivo permeation experiments of the optimized formula were conducted. Lastly, in vivo skin deposition of MTX from both the optimized formula and MTX solution was performed in rats. Besides, histopathological changes in rat skin were assessed. The optimized MTX ultra-permeable niosomal formula demonstrated spherical morphology, with an EE% of 65.16% and a PS of 453.6nm. The optimized formula showed better physical stability in comparison with that of the same composition but lacking PVA. The cell viability studies verified the superior cytotoxicity of the optimized formula, and the ex vivo permeation studies revealed its ability to improve the drug permeation. The optimized formula demonstrated a significant deposition of MTX in rat dorsal skin, and histopathological evaluation confirmed the tolerability of the optimized formula in rats upon topical application. Accordingly, ultra-permeable noisomes, as a stable nanosystem, could be promising for effective delivery of MTX.

Synthesis of Nitrogen Containing Biocompatible Non-ionic Surfactants and Investigation for Their Self-Assembly Based Nano-Scale Vesicles

Abstract Nonionic surfactants are increasingly interesting because of the solubility and release of drugs. Here, a synthesis of four nonionic nitrogen-containing surfactants is reported. In the synthesis, sulfonamide was reacted with alkyl halides of different lipophilicity. The synthesized nonionic surfactants were characterized by 1H NMR and mass spectroscopy. Their critical micelle concentration (CMC) was determined with a UV spectrophotometer. The self-assembly of surfactants to form drug-loaded, niosomal vesicles with Simvastatin as model drug was investigated. The resulting niosoaml vesicles were characterized by atomic force microscope (AFM), zeta-sizer, and UV spectrophotometer for shape, size, polydispersity index, zeta potential, and drug inclusion efficiency. Their biocompatibility has been determined by blood hemolysis and cell toxicity tests. The synthesized surfactants showed low CMC values and were able to form nano-sized round niosomal vesicles with a homogeneous population and surface negativity. Depending on the lipophilicity, they absorbed an increased amount of drug. The biocompatibility studies show that the surfactants are hemocompatible and non-toxic. The results of the study confirm that the synthesized nonionic surfactants are suitable for the solubilization and release of hydrophobic drugs as efficient novel biocompatible carriers.

Interaction between Gemini Dodecyl O-Glucosides-Based Multilayer Vesicles and β-Lactoglobulin: The Dominant Role of Surface Charge.

Novel Gemini dodecyl O-glucoside-based primary, secondary, and tertiary vesicles were developed in this work utilizing layer-by-layer deposition of polysaccharides (e.g., sodium carboxymethyl cellulose and chitosan), and their interaction with β-lactoglobulin (BLG) was carefully investigated. The increase of polysaccharide layers on primary vesicles led to a monotonic increase in size and consecutive reversal of surface charge. Polysaccharide deposition significantly retarded the vesicle aggregation and degradation of entrapped catechin laurate during storage. Steady-state fluorescence, isothermal titration calorimetry, and protein precipitation analyses revealed the surface charge dependence of the interactions between vesicles and a model milk protein BLG, which were much stronger when they were charged oppositely than when they presented the same type of surface charge. It was highlighted that the surface charge of vesicles could be tuned by differently charged coatings to accommodate to that of the milk proteins in the food matrix. This work will contribute to the practical application of niosomal vesicles loaded with bioactive compounds to fortify dairy products.

Dispersion analysis of niosomes different composition

The aim of this investigation was to study the variability of solutions of niosomes of various compositions under the influence of heating. For the analysis, the methods of scanning electron microscopy and processing of granulometric data were used. Experimental data on the sizes of niosomal vesicles of different compositions were statistically processed and interpreted from the point of view of the possibility of using a temperature factor to control the dispersion of the system. It has been shown that niosomes prepared on the basis of a nonionic surfactant, which is a group of dimethiconecopolyol substances that are esters of the polyethylene glycol and polydimethylsiloxane (PDMS) of the posterior bone, are more sensitive to the temperature factor, compared to niosomes based on sorbitan monostearate. So, for the first sample, the median size changed from 125 to 85 nm, and for the second sample from 790 to 560 nm. The data obtained made it possible to draw a conclusion about the relationship between the value of the specific surface calculated from the particle size distribution and the aggregative stability of niosomal dispersion.

Multifuntional role of liposome-mimicking vesicles – Potential nanoreactors and effective storehouses for hemoglobin

Liposome-mimicking niosomal vesicles were synthesized using a surfactant having high hydrophile : lipophile (HLB) value i.e. Brij S-20. The effect of Brij concentration, preparation method and Brij : Cholesterol ratio on the niosome structure was thoroughly investigated. Due to high HLB of the surfactant, a low Brij : Cholesterol ratio leads to a more compact niosome structure. Fluorescence studies with diphenyl hexatriene (DPH) and a coumarin dye (C-153) indicate disruption of bilayer integrity of niosomes upon increase of temperature. More significantly, the niosomes show two important functions: (i) they can function as very efficient nanoreactors for synthesis of gold nanoparticles (GNPs); (ii) they also serve as “effective storehouses” for the physiologically important protein hemoglobin (Hb). In niosomes with 1:1 Brij : Cholesterol ratio, small highly crystalline GNPs are formed in the bilayer and larger ones in the aqueous core, thus leaving the surface free for further functionalization. The protein-surfactant interaction has also been studied in detail with an aim to understand the role of the niosomal bilayers in maintaining protein stability. It has been inferred from fluorescence and circular dichroism studies that Hb remains well encapsulated within the niosomal bilayers and is thus not exposed to external perturbations. Moreover, the Soret absorption of Hb is unaffected for several days upon encapsulation in niosomes. More importantly, Hb encapsulated in niosomes does not show significant denaturation even in presence of the well-known denaturant urea. One practical application of this may be in cases of acute renal failure where high urea concentration leads to severe anemia.

Preparation and assessment of prostaglandin E2 formulated with hydroxypropyl methyl cellulose and span 60 sustained release pessaries (vaginal suppositories)

Prostaglandin E2 (PGE2) is presented as a composed release pessaries utilizing two-polymer base. Hydroxypropyl methyl cellulose HPMC was used as a viscosity modifier and bioadhesive agent. Furthermore, nonionic surfactant span 60 (Sp 60) with or without cholesterol (CH) mixed with the base was used. The defined pessaries were assessed with regards to hardness, weight variation, softening time test and in vitro release studies. Every one of the formulations demonstrated consistency with pharmacopoeial benchmarks. In vitro expressed PGE2 disintegration was completed in phosphate buffer pH 4.5 utilizing USP XXII basket apparatus. TEM demonstrated that the PEG/Sp 60 bases formed niosomal vesicles upon hydration with water while the WH15/Sp 60 gave rise to emulsions when melted in phosphate buffer pH 4.5. Both types of the novel composed release pessaries (WH15/Sp 60 and WH15/HPMC) indicated moderate release rates for PGE2 when no CH detected and the recipes WH15/30%HPMC and PEGIII/SP60 being used as an effective matrix previously to give PGE2 sorting out the release. The outcomes also demonstrated that the CH addition to either WH15 or PEG base brought about increased PGE2 release rates. No interaction amongst PGE2 and excipients were observed from DSC studies. KEY WORDS : Pessary, PGE2, WH15, HMPC, Sp 60, Polymer, Sustained release, TEM Bull. Chem. Soc. Ethiop. 2018 , 32(2), 361-370. DOI: https://dx.doi.org/10.4314/bcse.v32i2.14

Tramadol HCl encapsulated niosomes for extended analgesic effect following oral administration

Currently, proniosomes are generating a lot of interest in the field of drug delivery. They are characterized by high stability, extended drug release, ease of manufacturing, and rapid reconstitution and transformation into niosomes. The current study investigated Tramadol HCl (TH) encapsulation into niosomal vesicles using proniosome technology. Tween 80 (T80), Span 80 (S80), Tween 40 (T40), and Span 40 (S40) formed the backbones for niosome preparations. Encapsulation efficiencies (EE), vesicular sizes, in vitro release, and pharmacological activities of niosomal TH preparations were evaluated based on results from the hot plate test. Size distribution analysis showed homogenous vesicles with varied particle size that could be attributed to surfactant type and cholesterol (Chol) content. TH EE increased as a function of the increase in surfactant hydrophilic–lipophilic balance. TH release increased from all formulations as Chol% was increased from 0% to 50%. TH release from niosomal formulations with different surfactant types at 10% Chol increased in a specific order: S80 > S40 > T80 > T40. Following oral administration of TH niosomes to mice, the analgesic effects showed significantly extended effects compared to the TH solution. Oral administration of TH-encapsulated niosomes could be useful for extending the drug's analgesic effects.

Pivotal role of Acitretin nanovesicular gel for effective treatment of psoriasis: ex vivo-in vivo evaluation study.

The goal of the current study was to explore the potential benefits of Acitretin (Act) nanovesicular gel as a prospective antipsoriatic topical delivery system counteracting the drug challenges in terms of its extremely low aqueous solubility, instability, skin irritation, and serious systemic adverse effects. Act-loaded niosomes were successfully developed, entirely characterized, and optimized. Further evaluation of the optimized formula was conducted regarding its stability and ex vivo cytotoxicity on different cell lines. The optimized niosomal vesicles were then incorporated in gel base matrix and investigated by sequential ex vivo (skin permeation and deposition) and in vivo (skin irritation and antipsoriatic activity using mouse tail model) experiments. The optimized Act-loaded niosomes (span 60:cholesterol molar ratio 1:1) were spherical in shape and exhibited the highest entrapment efficiency (90.32±3.80%) with appropriate nanosize and zeta potential of 369.73±45.45 nm and −36.33±1.80 mV, respectively. Encapsulation of the drug in the nanovesicles was further emphasized by differential scanning calorimetric and powder X-ray diffraction studies. After 3 months storage at 4±1°C, the optimized formula preserved its stability. Act nano niosomal gel produced a remarkable enhanced ex vivo permeation profile up to 30 h and significant drug deposition in the viable epidermal–dermal layers compared with those of Act gel. The pronounced antipsoriatic activity of the medicated nano niosomes was proved ex vivo in HaCaT cells (a keratinocyte cell line). Topical application of Act nano niosomal gel to mouse tail model further established its distinct in vivo antipsoriatic superiority in terms of significantly higher orthokeratosis, drug activity, and reduction in epidermal thickness compared with the control and other gel formulations. Also, negligible skin irritation and better skin tolerability of Act nanovesicular gel were revealed by primary irritation index and histopathologic examination.

Synthesis of Sulfur‐Based Biocompatible Nonionic Surfactants and Their Nano‐Vesicle Drug Delivery

AbstractNonionic surfactants are capable of forming nano‐range vesicles upon self‐assembling in an aqueous medium. These vesicles are highly stable, low in toxicity, and cost‐effective. Owing to their ability to solubilize both hydrophilic and hydrophobic substances, they are of great interest for drug solubilization and delivery. This study describes the synthesis and characterization of two new nonionic surfactants and their screening for biocompatibility and drug loading potentials in nano‐scale niosomal vesicles. They were characterized through mass spectroscopy, 1HNMR, and FT‐IR. Their critical micelle concentration (CMC) was investigated using UV–vis spectrophotometry. The biocompatibility study was carried out through blood hemolysis and in vitro cytotoxicity assays. The surfactants have very low CMC values, are highly hemo‐compatible, and were nontoxic when tested against a cell culture. They were able to form nano‐range niosomal vesicles with large variation in their size. Both new surfactants were able to encapsulate increased amounts of the drug, in this case clarithromycin. The chemical nature of the drug remained intact in the niosomal vesicles. The results suggest that these nonionic surfactants could be promising drug delivery vehicles.

Formulation and optimization of lacidipine loaded niosomal gel for transdermal delivery: In-vitro characterization and in-vivo activity

The aim of the present research work is to formulate lacidipine (LAC) loaded niosomes formulation for the management of hypertension by thin film hydration technique. The developed formulations were statistically optimized by four factors, three levels Box–Behnken design and were evaluated for vesicle size, entrapment efficiency, and flux. The optimized LAC niosomes was further evaluated for permeation depth by confocal laser scanning microscopy (CLSM) and converted to gel formulation. Further, the optimized LAC niosomes gel was evaluated for ex-vivo permeation study, skin irritation study, stability study and pharmacodynamics study. The optimized LAC niosomes formulation showed vesicle size, entrapment efficiency and flux value of 676.98±10.92nm, 82.77±4.34% and 38.43±2.43μg/cm2/h respectively, with spherical morphology. The comparative CLSM study showed that optimized LAC niosomes formulation has shown maximum permeation (70.75μm) as compare to LAC liposomes formulation (58.26μm). The optimized LAC niosomes gel showed skin permeation enhancement of 2.15 times as compare to control gel. Furthermore, in vivo antihypertensive activity showed significantly higher (p<0.001) reduction in blood pressure compared to oral suspension. Indeed, it was found that niosomal vesicles represented to be an efficient nano vesicular carrier for transdermal delivery of lacidipine.

Dorzolamide Loaded Niosomal Vesicles: Comparison of Passive and Remote Loading Methods.

Glaucoma is a common progressive eye disorder and the treatment strategies will benefit from nanoparticulate delivery systems with high drug loading and sustained delivery of intraocular pressure lowering agents. Niosomes have been reported as a novel approach to improve drug low corneal penetration and bioavailability characteristics. Along with this, poor entrapment efficiency of hydrophilic drug in niosomal formulation remains as a major formulation challenge. Taking this perspective into consideration, dorzolamide niosomes were prepared employing two different loading methodologies (passive and remote loading methods) and the effects of various formulation variables (lipid to drug ratio, cholesterol percentage, drug concentration, freeze/thaw cycles, TPGS content, and external and internal buffer molarity and pH) on encapsulation efficiency were assessed. Encapsulation of dorzolamide within niosomes increased remarkably by the incorporation of higher cholesterol percentage as well as increasing the total lipid concentration. Remote loading method showed higher efficacy for drug entrapment compared to passive loading technique. Incorporation of TPGS in bilayer led to decrease in EE; however, retarded drug release rate. Scanning electron microscopy (SEM) studies confirmed homogeneous particle distribution, and spherical shape with smooth surface. In conclusion, the highest encapsulation can be obtained using phosphate gradient method and 50% cholesterol in Span 60 niosomal formulation.

Hydrophilically modified self-assembling α-tocopherol derivative as niosomal nanocarrier for improving clarithromycin oral bioavailability

Synthesis of biocompatible and cost-effective novel nonionic surfactants from renewable resources has been the subject of greater scientific interest for enhancing the bioavailability of less water-soluble drugs. The present study focuses on the synthesis of α-tocopherol-based novel biocompatible nonionic surfactant and its evaluation for forming clarithromycin-loaded niosomal drug delivery system. α-tocopherol was hydrophilically modified through multistep reactions and characterized using mass and 1H NMR spectroscopic techniques. Drug-loaded niosomal vesicles were investigated for entrapment efficiency (%EE), size, polydispersity index (PDI), zeta potential (ζ) and morphology using LC-MS, dynamic light scattering (DLS) and atomic force microscopy (AFM). Blood haemolysis, cell culture and acute toxicity tests were performed to investigate its biocompatibility. In vivo oral bioavailability of clarithromycin loaded in niosomal formulation was studied in rabbits. The vesicles were spherical in shape and entrapped up to 75 ± 2.57% of the drug. They exhibited a homogeneous size distribution with a mean diameter of 245 ± 4.66 nm. The surfactant was quite haemocompatible, low cytotoxic and safe in mice. Improved oral bioavailability of clarithromycin was achieved when carried in α-tocopherol-based niosomes. Results obtained showed that the synthesized amphiphile is biocompatible and has excellent capability for formation of niosomal vesicles and enhancing oral bioavailability of less water-soluble drugs like clarithromycin.

Optimization of methotrexate loaded niosomes by Box–Behnken design: an understanding of solvent effect and formulation variability

Dermal drug delivery system which localizes methotrexate (MTX) in the skin is advantageous in topical treatment of psoriasis. The aim of the current study was to understand dilution effects and formulation variability for the potential formation of niosomes from proniosome gels of MTX. Box–Behnken’s design was employed to prepare a series of MTX proniosome gels of Span 40, cholesterol (Chol-X1) and Tween 20 (T20-X2). Short chain alcohols (X3), namely ethanol (Et), propylene glycol (Pg) and glycerol (G) were evaluated for their dilution effects on proniosomes. The responses investigated were niosomal vesicles size (Y1), MTX entrapment efficiency percent (EE%-Y2) and zeta potential (Y3). MTX loaded niosomes were formed immediately upon hydration of the proniosome gels with the employed solvents. Addition of Pg resulted in a decrease of vesicular size from 534 nm to 420 nm as Chol percentage increased from 10% to 30%, respectively. In addition, increasing the hydrophilicity of the employed solvents was enhancing the resultant zeta potential. On the other hand, using Et in proniosomal gels would abolish Chol action to increase the zeta potential value and hence less stable niosomal dispersion was formed. The optimized formula of MTX loaded niosomes showed vesicle size of 480 nm, high EE% (55%) and zeta potential of –25.5 mV, at Chol and T20 concentrations of 30% and 23.6%, respectively, when G was employed as the solvent. Hence, G was the solvent of choice to prepare MTX proniosomal gels with a maintained stability and highest entrapment.

Transdermal potential and anti-gout efficacy of Febuxostat from niosomal gel

Gout is a metabolic disorder which causes inflammation of the joints. The pain can be relieved by taking anti-inflammatory or pain-relieving medication. Febuxostat, a xanthine oxidase inhibitor is also used in the treatment of gout. It is a weak acid (pKa = 3.08) and is therefore, practically insoluble in water. Due to its limited solubility in water and susceptibility to enzymatic degradation in intestine and liver, its oral bioavailability is affected. The presence of food also decreases its maximum plasma concentration (Cmax) by 38–39%. Hence, transdermal route is preferred for its administration. In the present research, niosomal vesicles were selected for Febuxostat delivery because of their penetration enhancing ability. Niosomes containing Febuxostat were prepared using thin film hydration method. A 23 factorial design (DOE analysis) was carried out to reduce the number of experiments. Parameters contribution was determined using a 3-D response curve. Prepared optimized batch (F4) exhibited entrapment efficiency of 73.93 ± 0.75% and percent cumulative drug release of 83.03 ± 0.07%. Transmission Electron Microscopy (TEM) revealed vesicular, spherical particles with a smooth surface in the nano range. Niosomal gel of optimized batch (F4) was prepared incorporating 2% w/w carbopol 934. The ex-vivo permeation study was performed in the Franz diffusion apparatus using excised rat abdominal skin in phosphate buffer pH 7.4, which showed prolonged drug permeation of 80.37 ± 0.02%. In-vivo study of optimized Febuxostat niosomal gel NG (F4) on rabbits revealed better results than the standard (pure) Febuxostat. NG (F4) exhibited good stability throughout 90 days at different temperature and humidity.

Bosentan Monohydrate Vesicles Loaded Transdermal Drug Delivery System: In Vitro In Vivo Evaluation

This study elucidates the enhancement of the permeation of bosentan monohydrate through skin by encapsulating it in vesicles loaded transdermal delivery system. Niosomal vesicles were formulated by ether injection method. Formulation FN7 (span 60: cholesterol: poloxamer 401, 1.25:1:0.25) showed maximum entrapment efficiency of 96.7±0.037% and was optimized for loading in to transdermal system. Transdermal systems were formulated using both hydrophilic and hydrophobic polymers like HPMC, HEC and EC. Formulation F1 with HPMC was optimized based on in vitro release (99.21±1.45 %) and was further evaluated for ex-vivo permeation. The results indicate that the ex vivo release (98.13±1.65%) was as par with in vitro release and followed zero order super case- II transport mechanism. The in vivo studies were done on New Zealand male rabbits for oral and transdermal route. The results inferred no significant change in half-life of drug but a substantial difference in Tmax, AUC and MRT was observed in transdermal systems. A two fold increase in AUC was observed in transdermal route (18.609±7.251µg/ml/h) when compared to oral route (9.644±5.621µg/ml/h). A controlled release was attained up to 35h and reservoir effect was observed and this may be due to the barrier properties of skin. Drug encapsulated niosomes were released in to the skin by loosening the lipid layers and the surfactant acted as penetration enhancer. The study infers that niosomes loaded transdermal patches of bosentan monohydrate can enhance the bioavailability and provided controlled release for better therapeutic efficacy and safety of drug.

Creatinine-based non-phospholipid vesicular carrier for improved oral bioavailability of Azithromycin

Context: Novel, safe, efficient and cost effective nano-carriers from renewable resources have got greater interest for enhancing solubility and bioavailability of hydrophobic dugs.Objectives: This study reports the synthesis of a novel biocompatible non-phospholipid human metabolite "Creatinine" based niosomal delivery system for Azithromycin improved oral bioavailability.Methods: Synthesized surfactant was characterized through spectroscopic and spectrometric techniques and then the potential for niosomal vesicle formation was evaluated using Azithromycin as model drug. Drug loaded vesicles were characterized for size, polydispersity index (PDI), shape, drug encapsulation efficiency (EE), in vitro release and drug–excipient interaction using zetasizer, atomic force microscope (AFM), LC–MS/MS and FTIR. The biocompatibility of surfactant was investigated through cells cytotoxicity, blood hemolysis and acute toxicity. Azithromycin encapsulated in niosomes was investigated for in vivo bioavailability in rabbits.Results: The vesicles were spherical with 247 ± 4.67 nm diameter hosting 73.29 ± 3.51% of the drug. Surfactant was nontoxic against cell cultures and caused 5.80 ± 0.51% hemolysis at 1000 µg/mL. It was also found safe in mice up to 2.5 g/kg body weight. Synthesized surfactant based niosomal vesicles revealed enhanced oral bioavailability of Azithromycin in rabbits.Conclusions: The results of the present study confirm that the novel surfactant is highly biocompatible and the niosomal vesicles can be efficiently used for improving the oral bioavailability of poor water soluble drugs.

Enhancement of 8-methoxypsoralen topical delivery via nanosized niosomal vesicles: Formulation development, in vitro and in vivo evaluation of skin deposition

The aim of the present study is to enhance the skin penetration and deposition of 8-methoxypsoraln (8-MOP) via niosomal vesicles to increase its local efficacy and safety. 8-MOP niosomes were prepared by the thin film hydration method using Span 60 or Span 40 along with cholesterol at five different molar ratios. The obtained vesicles revealed high entrapment efficiencies (83.04–89.90%) with nanometric vesicle diameters (111.1–198.8nm) of monodisperse distribution (PDI=0.145–0.216), zeta potential values <−48.3mV and spherical morphology under transmission electron microscopy. Optimized niosomal formulations depicted a biphasic in vitro release pattern in phosphate buffer (pH 5.5)/ethanol (7:3v/v) and displayed good physical stability after storage for 6 months at room (20–25°C) and refrigeration (4–8°C) temperatures. The two optimized formulations were incorporated in 5% sodium carboxy methylcellulose based hydrogel matrix which showed optimum pH values (7.37–7.39), pseudoplastic with thixotropic rheological behavior and more retarded 8-MOP release, by 23.82 and 14.89%, compared to niosomal vesicles after 24h. In vitro drug permeation and deposition studies, using rat skins, revealed promoted penetration and accumulation of 8-MOP after 8h. The skin penetration was further confirmed in vivo by confocal laser scanning microscopy, after 2h application period using rhodamine-loaded niosomal hydrogels compared to plain rhodamine hydrogel, as a florescence marker. Therefore, enhanced permeation and skin deposition of 8-MOP delivered by niosomes may help in improving the efficacy and safety of long-term treatment with 8-MOP.

Sugar-based novel niosomal nanocarrier system for enhanced oral bioavailability of levofloxacin

Context: Vesicular systems have attracted great attention in drug delivery because of their amphiphilicity, biodegradability, non-toxicity and potential for increasing drug bioavailability.Objective: A novel sugar-based double-tailed surfactant containing renewable block was synthesized for preparing niosomal vesicles that could be exploited for Levofloxacin encapsulation, aiming to increase its oral bioavailability.Materials and methods: The surfactant was characterized by 1H NMR, mass spectroscopy and Fourier transform infrared spectroscopy (FT-IR). Its biocompatibility was studied against cell cultures and human blood hemolysis. In vivo acute toxicity was evaluated in mice. The vesicle morphology, size, drug-excipients interaction and entrapment efficiency (EE) were examined using atomic force microscope (AFM), dynamic light scattering (DLS), FT-IR and HPLC. Oral bioavailability studies of Levofloxacin in surfactant-based niosomal formulation were carried out using rabbits and plasma samples were analyzed using HPLC.Results and discussion: Vesicles were spherical in shape and the size was 190.31 ± 4.51 nm with a polydispersity index (PDI) of 0.29 ± 0.03. The drug EE in niosomes was 68.28 ± 3.45%. When applied on cell lines, high cell viability was observed even after prolonged exposure at high concentrations. It caused 5.77 ± 1.34% hemolysis at 1000 μg/mL and was found to be safe up to 2000 mg/kg. Elevated Levofloxacin plasma concentration was achieved when delivered with novel vesicles.Conclusion: The surfactant was demonstrated to be safe and effective as carrier of Levofloxacin. The study suggests that this sugar-based double-tailed nonionic surfactant could be promising nano-vesicular system for delivery and enhancing oral bioavailability of the hydrophobic Levofloxacin.

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.

Stabilization of natural canthaxanthin produced by Dietzia natronolimnaea HS-1 by encapsulation in niosomes

In this study, canthaxanthin (CTX) was extracted from Dietzia natronolimnaea HS-1 and encapsulated in niosomes, with the aim of improving its stability. Niosomal vesicles were prepared by hydrating mixtures of various nonionic surfactants, namely tween (60, 80) and span (60, 80), with cholesterol at different surfactant/cholesterol molar ratios (1.2:0.8, 1:1 and 0.8:1.2). Results showed vesicle mean diameter in the range 159–345 nm. All formulations showed a negative surface charge and entrapment efficiency in the range 32.7–81.2%. Niosomes prepared with span 60 in combination with cholesterol at 1:1 M ratio were small and uniform in size, with high entrapment efficiency values. The influence of pH (3, 5 and 7), light and temperature (4, 25 and 40 °C) on vesicle stability was evaluated by monitoring the CTX leakage on storage. Degradation of samples was found in all conditions, especially in the presence of light. The amount of CTX retained in the niosomes decreased on storage and was strongly affected by temperature. However, the addition of cholesterol to niosome formulations decreased degradation rate of CTX as a consequence of the reduced permeability of the niosomal bilayers. Overall results of the present study demonstrate a stability enhancement of CTX in niosomes.