Comparison of PLGA and lecithin/chitosan nanoparticles for dermal targeting of betamethasone valerate

Abstract

Poly(lactide-co-glycolide) (PLGA) and lecithin/chitosan (LC) nanoparticles were prepared to evaluate the difference in the behavior upon administration on skin, for steroidal treatment. For this purpose, betamethasone-17-valerate (BMV)-loaded nanoparticles with a narrow size distribution and high entrapment efficiency were prepared. Permeation studies showed that both polymeric nanoparticles enhanced the amount of BMV in epidermis, which is the target site of topical steroidal treatment, when compared with commercial formulation. 1.58-Fold increase was determined in the epidermis concentration of BMV by LC nanoparticles with respect to PLGA nanoparticles. Nanoparticles were diluted in chitosan gel (10%, w/w) to prepare suitable formulation for topical application. Accumulation from both gel formulations were found significantly higher than commercial formulation in skin layers (p?<?0.05). In addition, pharmacodynamic responses were also investigated as anti-inflammatory and skin-blanching parameters. Both formulations significantly improved these parameters although they contained 10 times less amount of BMV than commercial cream. Moreover, TEWL measurement exhibited no barrier function changes upon the application of nanoparticles on skin. Overall, both nanoparticles improved the localization of BMV within skin layers; but when compared with PLGA nanoparticles, the LC nanoparticles could be classified as a better candidate for topical delivery vehicle in the treatment of various dermatological inflammatory diseases.     

An investigation into the combination of low frequency ultrasound and liposomes on skin permeability

Antigen application onto skin that has been pre-treated with low frequency ultrasound leads to immunisation, and it was hypothesised that immunisation could be enhanced if antigens were entrapped within liposomes, the latter being known vaccine adjuvants. However, it has been suggested that liposomes can repair skin damage, which could limit antigen permeation and transcutaneous immunisation. The aim of the present work was therefore to investigate the influence of liposome application on subsequent: (i) in vitro antigen permeation through, and (ii) in vivo barrier properties of, ultrasound-treated skin. Sonication was conducted using either phosphate buffered saline (PBS) or an aqueous solution of sodium dodecyl sulphate (SDS) as the coupling medium, and rats were used as the animal models. Liposome application to sonicated skin reduced antigen penetration and transepidermal water loss (TEWL, used as an indication of skin integrity) when the skin had been sonicated using PBS coupling medium. The influence of liposome was evident within 5 min of its application, and smaller liposomes were more effective at repairing skin disruption caused by sonication. Such skin repair did not, however, take place when the skin had been sonicated in the presence of SDS (which caused greater skin disruption), and changes in in vitro antigen permeation and in vivo TEWL were negligible. Skin repair by liposomes seems to depend on the extent of the disruption caused by ultrasound application.     

Solid lipid nanoparticles-loaded topical gel containing combination drugs: an approach to offset psoriasis

Aim: The primary aim of present work was to develop effective combination drug therapy for topical treatment of psoriasis.

Methods: Betamethasone dipropionate and calcipotriol loaded solid lipid nanoparticles (CT-BD-SLNs) were prepared by hot melt high shear homogenization technique, which were then incorporated in Carbopol gel matrix. The anti-psoriatic potential was tested by sequential in vitro (skin permeation and dermal distribution, anti-proliferative effect in HaCaT cells) and in vivo (Draize patch irritation, transepidermal water loss (TEWL) and anti-psoriatic mouse tail studies) experiments.

Results: A negligible amount in receptor compartment, yet confined distribution of drugs to epidermal and dermal region of skin was observed in case of SLNs, which is essential for safe and effective anti-psoriatic therapy. Draize patch test and TEWL demonstrated negligible skin irritation and better skin tolerability of SLNs. The in vitro HaCaT cell line study demonstrated that SLNs delayed the abrupt growth of keratinocytes, while in vivo mouse tail model showed that SLNs gel significantly decreased the epidermal thickness and increased melanocyte count in comparison to commercial Daivobet® ointment.

Conclusions: The developed SLNs gel is expected to be potential strategies for treatment of psoriasis and other topical diseases.     

Influence of Liposome Bilayer Fluidity on the Transport of Encapsulated Substance into the Skin as Evaluated by EPR

Purpose. The influence of liposome composition on the bilayer fluidity and on the transport of encapsulated substance into the skin was investigated. Methods. Multilamellar vesicles (MLV) from dipalmitoylphosphatidylcholine (DPPC) or dimyristoylphosphatidylcholine (DMPC) with various amounts of cholesterol were prepared by the film method and characterised by photon correlation spectroscopy and electron paramagnetic resonance (EPR) methods. The transport of the hydrophilic spin probe encapsulated in MLV into pig ear skin was investigated by EPR imaging methods. The bilayer domain structure was studied by fitting the lineshape of the experimental EPR spectra with the spectra calculated by the model, which takes into account the heterogeneous structure of the bilayer with several coexisting domains. Results. Cholesterol strongly influences the entrapped volume of liposomes, the domain structure of the lipid bilayer, and the transport of hydrophilic spin probe into the skin. Transport was not observed for liposomes composed of phospholipid:cholesterol 1:0 or 9:1 (mol:mol), not even above the phase transition temperature from the gel to the liquid crystalline phase of DMPC. A significant delivery of hydrophilic spin probe was observed only if there was 30 or 50 mol% of cholesterol in the liposome bilayer. Conclusions. It can be concluded that the domain structure of the liposome bilayer is more important for the delivery of encapsulated substance into the skin than the liquid crystalline phase of the pure phospholipids bilayer.     

乌拉草总黄酮脂质体凝胶剂的制备工艺研究

目的 优化乌拉草总黄酮脂质体凝胶剂的制备工艺,并进行质量评价。方法 乙醇注入法制备乌拉草总黄酮（CMTF）脂质体,以包封率为指标,正交试验优化处方;以脂质体凝胶剂的外观、涂展性、均匀度、黏稠度等综合评分为指标,采用Box-Behnken响应面法优化CMTF脂质体凝胶的处方及制备工艺。通过观察性状、pH值、铺展性及可洗除性,以及离心试验、耐寒及耐热试验,考察CMTF脂质体凝胶稳定性;观察其对大鼠正常及破损皮肤的刺激性。结果 CMTF脂质体的最佳制备工艺为：大豆磷脂与胆固醇的质量比为5：3,大豆磷脂与CMTF的质量比为4：1,注入体积比例1：10;平均包封率为89.41%,粒径为（119.7±3.82）nm,Zeta电位为（-20.80±0.40）mV。CMTF脂质体凝胶剂的最佳处方为：1 g CMTF脂质体、2 g卡波姆940、20 g甘油、2 g三乙醇胺、10 mL水,该脂质体凝胶剂的稳定性良好,无皮肤刺激性。结论 优化后的CMTF脂质体凝胶制备工艺简单,质量稳定,为CMTF经皮制剂的开发提供依据。     

In Vitro-In Vivo Myotoxicity of Intramuscular Liposomal Formulations

Purpose. The first objective was to study the in vitro myotoxicity of empty liposomes and to examine whether liposome size, charge and fluidity affect liposome myotoxicity. The second objective was to investigate the effect of liposomal encapsulation on the in vitro and in vivo myotoxicity of loxapine compared to the loxapine commercial preparation (Loxitane^®). Methods. The in vitro myotoxicity of empty liposomes and loxapine liposomes was evaluated by the cumulative efflux of the cytosolic enzyme creatine kinase (CK) from the isolated rat extensor digitorum longus (EDL) muscle over a 2 hour period. In the in vivo studies, the area under plasma CK curve over 12 hours was used to evaluate muscle damage. Results. The in vitro myotoxicity for all empty liposomal formulations was not statistically different from negative controls (untreated control muscles and normal saline injected muscles). However, these empty liposomal formulations were significantly less myotoxic than the positive controls (muscles injected with phenytoin and muscle sliced in half). In vitro-in vivo studies showed that the liposomal encapsulation of loxapine resulted in significant (P < 0.05) reduction in myotoxicity (80% in vitro and 60% in vivo) compared to the commercially available formulation which contains propylene glycol (70% V/V) and polysor-bate 80 (5% W/V) prepared at equal concentration. Conclusions. Results indicate that empty liposomes do not induce myotoxicity. Furthermore, liposomal size, charge and fluidity do not affect myotoxicity. In addition, in vitro and in vivo studies have demonstrated that liposomal encapsulation of loxapine can reduce myotoxicity compared to a formulation containing organic cosolvents.     

Nasal in-situ gels for delivery of rasagiline mesylate: improvement in bioavailability and brain localization

Abstract

Intranasal thermosensitive gel for rasagiline mesylate (RM) was developed for effective treatment of Parkinson’s disease. Intranasal gels were prepared by combination of poloxamer 407 and poloxamer 188 (1:1) with mucoadhesive polymers (carbopol 934?P and chitosan). The formulations were evaluated for sol–gel transition temperature, in-vitro drug release and in-vivo mucociliary transit time. Further, optimal intranasal gel formulations were tested for in-vivo pharmacokinetic behavior, nasal toxicity studies and brain uptake studies. It was found that optimal formulations had acceptable gelation temperature (28–33?°C) and adequate in-vitro drug release profile. Pharmacokinetic study in rabbits showed significant (p?<?0.05) improvement in bioavailability (four- to six-folds) of the drug from intranasal gels than oral solution. Chronic exposure studies in Wistar rats showed that these intranasal gels were non-irritant and non-toxic to rat nasal mucosa. Estimation of RM in rat brain tissue showed significant (p?<?0.01) improvement in uptake of RM form intranasal gel formulations than nasal solution.     

Pharmacokinetic and Pharmacological Profiles of Free and Liposomal Recombinant Human Erythropoietin After Intravenous and Subcutaneous Administrations in Rats

Purpose. Recombinant human erythropoietin (Epo) is used frequently through intravenous (i.v.) and subcutaneous (s.c.) administration for the clinical treatment of the last stage of renal anemia. We encapsulated Epo in liposomes to develop an alternative administration route. The purpose of our study was to evaluate the pharmacokinetics and the pharmacological effects of liposomal Epo in comparison with the Epo after i.v. and s.c. administration to rats. Methods. Epo was encapsulated in liposomes composed of dipalmitoylphosphatidylcholine (DPPC) and soybean-derived sterol mixture (SS) prepared by the reversed-phase evaporation vesicle method. After filtration through a 0.1 m polycarbonate membrane, liposomes were gel filtered (Epo/liposomes). Results. Epo/liposomes showed higher pharmacological activity than Epo/liposomes before gel filtration after i.v. administration to rats. Non-encapsulated Epo lost its activity, whereas encapsulated Epo in liposomes retained it. The pharmacological effects of Epo/liposomes were greater than those of Epo after i.v. administration. Epo/liposomes afforded 3–9 times higher AUC, lower clearance and lower steady-state volume of distribution than Epo after both i.v. and s.c. administrations. Epo/liposomes had an improved pharmacokinetic profile compared with Epo. S.c. administration of Epo/liposomes at 7 h may penetrate primarily (40% of dose) through the blood as a liposome and partly (7% of dose) in lymph. Conclusions. Epo/liposomes may reduce the frequency of injections required for a certain reticulocyte effect in comparison to Epo. The lower clearance of Epo/liposomes may increase the plasma concentrations of Epo, which increases the efficacy.     

Aggregation of unilamellar lecithin liposomes induced by cyclosporin

Abstract

Small unilamellar [¹⁴C]lecithin liposomes prepared in the presence of cyclosporin sedimented at 12000 g. Sepharose 4B gel filtration of the resuspended pellet and supernatant yielded identical peaks consisting of small unilamellar liposomes containing cyclosporin. The column retained 40–50 per cent of ¹⁴C-labelled liposomes prepared in the presence of cyclosporin as liposome aggregates.     

Physicochemical characterization and skin permeation of liposome formulations containing clindamycin phosphate

This study was undertaken to evaluate the physicochemical properties and skin permeation of liposome formulations containing clindamycin phosphate (CP), especially when charge was imparted to the liposome. Five different liposome formulations were prepared using Phospholipon 85G (PL) and cholesterol (CH) by conventional lipid film hydration technique. Molar ratio of CH to PL was varied in the range of 0.16–1.0. Charged liposomes were prepared in the same way with addition of 1,2-dioleoyl-3-trimethylammonium-propane chloride salt (DOTAP) and 1,2-dimyristoyl-sn-glycero-3-phosphate monosodium salt (DMPA) as charge carrier lipid for cationic or anionic charge of the liposome, respectively. Fresh full-thickness mice skin was taken and used for skin permeation study using Keshary-Chien diffusion cell with 1.77 cm² diffusion area at 37°C. All liposome formulations prepared showed homogeneous size distribution with mean particle size of about 1 μm or less. Among the five liposome formulations prepared, formulation with the molar ratio of 0.5 showed the best result in the physicochemical properties such as polydispersity index, entrapment efficiency, size evolution, and ability of the liposome to retain CP as of entrapped in the vesicles. Charge-impartation of the formulation with cationic charge carrier lipid resulted in additional benefit in terms of inhibition of size evolution, the ability of the liposome to retain CP in the vesicles, and skin permeation. Steady state flux of the drug through the mice skin in the cationic liposome vesicles was 0.75 ± 0.01 μg/cm²h while that in the control (dissolved into mixed alcohol solution) was 0.17 μg/cm²h. One half molar ratio of CH to PL was optimal in terms of physicochemical properties of the liposome formulation containing CP, and incorporation of cationic charge carrier lipid appeared to provide additional benefits for the stability of the liposome formulation and skin permeation of the drug.     

Characterization and skin permeation of ketoprofen-loaded vesicular systems

PurposeTo determine the effect of elasticity on the skin permeation of ketoprofen from surfactant-based vesicular formulations and elastic liposomes.MethodsKetoprofen-loaded surfactant-based vesicles and elastic liposomes were prepared by sonication. Citric buffer (at pH 3.0) was used as rehydration buffer. Characterization studies of the prepared liposomal formulations were performed by dynamic light scattering, extrusion, and ¹H and ³¹P nuclear magnetic resonance (NMR) spectroscopy. Ketoprofen transport studies across human skin were performed for all formulations.ResultsStable ketoprofen-loaded formulations were prepared. Addition of an edge activator, in the absence of the drug, increased the elasticity of the vesicles and liposomes. Ketoprofen loading reduced the elasticity of the liposomes and surfactant-based-vesicles. However, at saturation, the elasticity was still higher than that in the absence of the edge activator and ketoprofen, except for ketoprofen-loaded liposomes with Span 80. NMR studies revealed that the ketoprofen molecules were entrapped in a vesicle bilayer in all vesicular formulations and that the ketoprofen molecules affected the phosphate mobility in the liposomal formulations. Ketoprofen transport studies across human skin clearly showed that the surfactant-based vesicular formulations were superior to the elastic liposomal formulations.ConclusionSurfactant-based vesicles enhance ketoprofen transport across human skin, while no enhancement of ketoprofen was observed when loaded in elastic liposomes.     

High-efficient nano-carrier gel systems for testosterone propionate skin delivery

Abstract

The purpose of the current investigation was to evaluate the skin delivery potential of the different nano-carrier gels including liposomal gel, ethosomal gel and microemulsion gel bearing testosterone propionate (TP) as a testosterone deficient therapy. The prepared nano-particles were characterized for their shape, particle size distribution and zeta potential. In vitro skin permeation and in vivo transdermal delivery of nano-carrier gels were studied with the Franz diffusion cells and confocal laser scanning microscopy (CLSM). The results showed that all of nano-particles were almost spherical with low polydispersity and nano-metric size range from 40 to 200?nm. TP ethosomal gel also provided an enhanced transdermal flux of 7.64?±?1.4?μg/cm²/h and a decreased lag time of 0.69?h across rat skin as compared with the other two formulations. The skin penetration efficiency of TP nano-carrier gels also revealed that TP ethosomal gel would enhanced penetration of rhodamine red (RR)-loaded formulation to the deeper layers of the skin (268?µm) than the liposomal gel (192?µm) and microemulsion gel (228?µm). This study demonstrated TP ethosomal gel is a promising nano-carrier for delivering TP through the skin.     

Polymeric microparticles-based formulation for the eradication of cutaneous candidiasis: development and characterization

Abstract

Cutaneous candidiasis is a common topical fungal infection which may be more prominent in patients associated with AIDS. It is usually treated by conventional formulations such as cream, gel, which show various adverse effects on skin along with systemic absorption. To overcome these drawbacks, various novel drug delivery systems have been explored. Poly(lactic-co-glycolic acid) (PLGA)-based microparticulate systems have shown good dermal penetration after topical application. Therefore, in the present study clotrimazole-loaded PLGA microspheres were prepared for targeted dermal delivery. Microspheres were prepared by using a single emulsification (oil-in-water, O/W) evaporation technique and characterized for different parameters. Prepared microparticulate systems were dispersed in Carbopol 934® gel and antifungal activity was carried out on experimentally induced cutaneous candidiasis in immunosuppressed guinea pigs. Particle size of optimized formulation was 2.9?µm along with 74.85% entrapment of drug. Skin retention studies revealed that drug accumulation in the skin was higher with microspheres gel as compared to marketed gel. Confocal microscopy of skin further confirmed penetration of microspheres up to 50?µm into the dermal region. In-vivo antifungal activity studies demonstrated that microsphere gel showed better therapeutic activity, lowest number of cfu/ml was recorded, as compared to marketed gel after 96?h of application. Based on the results of the study, it can be concluded that PLGA microparticles may be promising carriers to deliver clotrimazole intradermally for the treatment of invasive fungal infections.     

Nanoparticles laden in situ gel of levofloxacin for enhanced ocular retention

Abstract

Availability of proper concentration of medicament on to the corneal surface is a challenging task. Many novel formulations, i.e. hydrogels, nanoparticles, ocuserts, etc. had been tested to improve ocular bioavailability, out of which our group found, in situ gel and polymeric nanoparticle are the most interesting approach to achieve ocular retention. We found that in situ gel stay only for 12?h and poly(lactic-co-glycolic acid (PLGA) nanoparticles are non mucoadhesive in nature so we try to combine both these formulations and termed it as “Nanoparticle laden in situ gel”. Here we prepare nanoparticle laden in situ gel containing levofloxacin encapsulated PLGA nanoparticle, incorporated in chitosan in situ gel and evaluated its ocular retention by gamma scintigraphy in rabbits. The observations of acquired gamma camera images showed good retention over the entire precorneal area. From static and dynamic gamma scintigraphy evaluation, we can be interpret that developed nanoparticle laden in situ gel formulation cleared at a very slow rate and remained at corneal surface for longer duration than marketed formulation, in situ gel and nanosuspension alone.     

A new vaginal delivery system of amphotericin B: a dispersion of cationic liposomes in a thermosensitive gel

Amphotericin B (AmB) is used in the treatment of fungal infections; however, its clinical use is limited by its toxic side effects. In this study, AmB-loaded cationic liposome gels were formulated with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and cholesterol (CH) at a molar ratio of DOPE:DOTAP:CH?=?4:5:1 in thermosensitive gel composed of poloxamer 407 (P407) and poloxamer 188 (P188). To enhance the solubility of AmB, 6 mol% of distearoyl phosphatidyl ethanolamine–polyethylene glycol was added prior to encapsulation of the drug into liposomes. Scanning electron microscopy was used to observe the AmB encapsulated cationic liposome gels. In vitro release, stability and cytotoxicity of AmB in cationic liposome gels were evaluated. The particle size and zeta potential of AmB-loaded liposomes were in the range of 400–500?nm and 40–60 mV, respectively. The thermosensitive gel at the ratio of P407:P188?=?15:15 (w/w) gelled at 37°C, approximating body temperature. Encapsulation efficiency of AmB was ～50–60%, which was influenced by the ratio of AmB to lipid. Moreover, AmB-loaded cationic liposome gels were more stable and less toxic than free AmB. From these results, cationic liposome gel formulations may be useful for vaginal delivery of AmB.     

Microsponges enriched gel for enhanced topical delivery of 5-fluorouracil

Abstract

This study aimed to develop microsponges based topical gel formulation of 5-Fluorouracil (5-FU) for the treatment of skin cancer with enhanced skin deposition and reduced skin irritation potential. Microsponges were prepared by Quasi-emulsion solvent diffusion method using ethyl cellulose and Eudragit RL 30?D; and was optimised through detailed in vitro characterisation. Brunauer–Emmett–Teller (BET) analysis demonstrated higher surface area (2.4393?m²/g) and pore volume of developed microsponges formulation. Optimised formulation showed better thixotropic and texture properties compared to commercial cream formulation, used as control for comparison purpose. Further, the optimised formulation demonstrated 5.5-fold increase in skin deposition documented via in-vivo local bioavailability study, with significant reduction in skin irritation compared to the commercial formulation. Hence, the developed microsponges based formulation seems to be a viable alternative with enhanced topical delivery of 5-FU as compared to the commercial formulation.     

Formulation of Liposome for topical delivery of arbutin

The aims of this study were to encapsulate arbutin (AR) in liposome to enhance the skin-whitening activity, and to investigate the effect of liposome formulation on the entrapment efficiency (EE%), skin permeation rate and skin deposition. The liposomes were prepared by a film dispersion method with several different formulations and were separated from the solution by using the gel-filtration method. The physical (size distribution, morphology) and chemical (drug entrapment efficiency, hairless mouse skin permeation and deposition) properties of liposomes were characterized. The entrapment efficiency in all liposome formulations varied between 4.35% and 17.63%, and was dependent on the lipid content. The particle sizes of liposomes were in the range of 179.9-212.8 nm in all liposome formulations. Although the permeation rate of AR in the liposome formulations decreased compared with AR solution, the deposition amount of AR in the epidermis/dermis layers increased in AR liposomal formulation. These results suggest that liposomal formulation could enhance the skin deposition of hydrophilic skin-whitening agents, thereby enhancing their activities.     

Cholate-Induced Disruption of Calcitonin-Loaded Liposomes: Formation of Trypsin-Resistant Lipid-Calcitonin-Cholate Complexes

Purpose. The work was performed to obtain a better understanding why the oral administration of calcitonin (CT)-loaded liposomes to rats results in a hypocalcemia, while liposomes are normally disrupted in the gastro-intestinal tract and cannot protect the hormone from enzymatic digestion. Methods. In vitro comparisons between the stability of calcein and CT-loaded liposomes in the presence of cholate solutions led to an interpretation of the results observed. By means of gel filtration, turbidimetry, and fluorescence measurements, the interactions between CT and lipids were studied after sonicated liposomes had been broken down by cholate. Results. Experiments showed that CT in the external medium of a liposome suspension had no effect on the vesicles. Gel filtration of cholate-treated liposomes loaded with calcein and CT resulted in a total separation of calcein from the lipid fraction for detergent concentrations higher than 4 mM. However, 50% of the CT was reencapsulated even when the cholate-to-phospholipid molar ratio was increased up to 100. Incubation of cholate-solubilized liposomes with 1% trypsin resulted in a partial CT-breakdown. Conclusions. These results strongly suggest that during membrane solubilization by cholate, lipid-CT complexes are formed which retain most of the CT initially embedded in the liposomal membrane, and which offer some protection to CT under the action of trypsin. The existence of these complexes could be one of the reasons for the reported hypocalcemia in rats after oral administration of CT-loaded liposomes.     

Effect of Particle Size and Charge on the Disposition of Lipid Carriers After Intratumoral Injection into Tissue-isolated Tumors

Purpose. Pharmacokinetic properties of various lipid carriers (liposome and emulsions) after intratumoral injection were studied in perfusion experiments using tissue-isolated tumor preparations of Walker 256 carcinosarcoma. Methods. Four types of lipid carriers, large emulsion (254 nm), small emulsion (85 nm), neutral liposomes (120 nm) and cationic liposomes (125 nm) were prepared. We quantified their recovery from the tumor, leakage from the tumor surface and venous outflow after intratumoral injection into perfused tissue-isolated tumors, and analyzed venous appearance curves based on a pharmacokinetic model. Results. In contrast to the small emulsion and neutral liposomes, which immediately appeared in the venous outflow perfusate following intratumoral injection, the appearance of the cationic liposomes and the large emulsion was highly restricted, clearly demonstrating that intratumoral clearance of these formulations can be greatly retarded by the cationic charge and large particle size, respectively. The venous appearance rate-time profiles were fitted to equations derived from a two-compartment model by nonlinear regression analysis. When the calculated parameters were compared among these four formulations, the venous appearance rate did not exhibit such a large difference; however, the rate of transfer from the injected site to the compartment which involves clearance by venous outflow was all very different. Conclusions. The results of this study indicate that the determining factor which alters the pharmacokinetic properties of these lipid carriers after intratumoral injection is not the rate of transfer from the interstitial space to the vascular side but the rate of intratumoral transfer from the injection site to the well-vascularized region.     

Nanoemulsion gel-based topical delivery of an antifungal drug: in vitro activity and in vivo evaluation

Abstract

Objective: In this study, attempt has been focused to prepare a nanoemulsion (NE) gel for topical delivery of amphotericin B (AmB) for enhanced as well as sustained skin permeation, in vitro antifungal activity and in vivo toxicity assessment.

Materials and methods: A series of NE were prepared using sefsol-218 oil, Tween 80 and Transcutol-P by slow spontaneous titration method. Carbopol gel (0.5%?w/w) was prepared containing 0.1%?w/w AmB. Furthermore, NE gel (AmB-NE gel) was characterized for size, charge, pH, rheological behavior, drug release profile, skin permeability, hemolytic studies and ex vivo rat skin interaction with rat skin using differential scanning calorimeter. The drug permeability and skin irritation ability were examined with confocal laser scanning microscopy and Draize test, respectively. The in vitro antifungal activity was investigated against three fungal strains using the well agar diffusion method. Histopathological assessment was performed in rats to investigate their toxicological potential.

Results and discussion: The AmB-NE gel (18.09?±?0.6?µg/cm²/h) and NE (15.74?±?0.4?µg/cm²/h) demonstrated the highest skin percutaneous permeation flux rate as compared to drug solution (4.59?±?0.01?µg/cm²/h) suggesting better alternative to painful and nephrotoxic intravenous administration. Hemolytic and histopathological results revealed safe delivery of the drug. Based on combined results, NE and AmB-NE gel could be considered as an efficient, stable and safe carrier for enhanced and sustained topical delivery for AmB in local skin fungal infection.

Conclusion: Topical delivery of AmB is suitable delivery system in NE gel carrier for skin fungal infection.