title: Statistically designed nonionic surfactant vesicles for dermal delivery of itraconazole: characterization and in vivo evaluation using a standardized Tinea pedis infection model.
abstract: The study aims to statistically develop a hydrogel of itraconazole loaded nonionic surfactant vesicles (NSVs) for circumventing the shortcomings and adverse effects of currently used therapies. Influential factors were screened using first-order Taguchi design, thereafter, optimization was performed via D-optimal design involving screened factors (surfactant type, content and molar ratio of cholesterol: surfactant). Response variables investigated were percent drug entrapment, vesicle size, drug skin retention and permeation in 6h. Suspensions of NSVs were gelled to improve topical applicability. Characterization of formulations was performed using vesicle shape, size, surface charge, texture analysis and rheology behavior. Ex vivo studies in rat skin depicted that optimized formulation augmented drug skin retention and permeation in 6h than conventional cream and oily solution of itraconazole. Standardized Tinea pedis model in Wistar rats exhibited in vivo antifungal efficacy of optimized formulation, observed in terms of physical manifestations, fungal-burden score and histopathological profiles. Also, a unique investigation involving studying local oxidative stress of infected paw skins as an indicator of fungal infection was performed. Rapid alleviation of infection in animals treated with optimized hydrogel was observed in comparison to commonly prescribed therapies. Therefore, the optimized NSVs may be a promising and efficient alternative to available antifungal therapies.
authors: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India.
authors: Neeraj
authors: N
authors: Kumar
authors: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India. Electronic address: shishugoindi@yahoo.co.in.
authors: Shishu
authors: S
authors: Goindi
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D015195:Drug Design; D005260:Female; D006601:Hexoses / Q000737:chemistry; D017964:Itraconazole / Q000008:administration & dosage* / Q000737:chemistry; D018384:Oxidative Stress; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D012869:Skin Absorption; D013501:Surface-Active Agents / Q000737:chemistry; D014008:Tinea Pedis / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology
chemical_list: D000935:Antifungal Agents; D006601:Hexoses; D013501:Surface-Active Agents; D017964:Itraconazole; C061705:sorbitan monopalmitate; D002784:Cholesterol; C009298:sorbitan monostearate
keywords: D-optimal; Itraconazole; Nonionic surfactant vesicles; Optimization; Oxidative stress