title: New perspectives in the topical delivery of optimized amphotericin B loaded nanoemulsions using excipients with innate anti-fungal activities: A mechanistic and histopathological investigation.
abstract: This study aimed to develop nanoemulsions (NEs) for the topical delivery of Amphotericin B using lipids and surfactants with innate antifungal activity. NEs were formulated by a slow spontaneous titration method and characterized for particle size, polydispersity index, zeta potential, zone of inhibition (ZOI), in vitro release, enhanced ex vivo rat skin permeation-deposition, hemolysis followed by interaction with the skin using scanning electron microscopy, and histopathology. The ZOI values of the optimized NEs (ANE3) were 21.8±1.5 and 19.7±1.2 mm against A. fumigatus and C. albicans, respectively. The explored excipients and optimized ANE3 elicited hemo-biocompatibility. ANE3 exhibited in vitro sustained release and an enhanced flux value (21.62±1.6 μg/cm2/h) as compared to the drug solution and Fungisome without displaying toxicity. Conclusively, ANE3 could be a promising therapeutic approach with enhanced efficacy and safety for treating a wide range of fungal infections topically.
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India; Faculty of Pharmacy, S. Sinha College, Aurangabad, Bihar, India.
authors.forename: Afzal
authors.initials: A
authors.lastname: Hussain
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India.
authors.forename: Sima
authors.initials: S
authors.lastname: Singh
authors.affiliation: Northeastern University, Department of Chemical Engineering, Boston, MA, USA. Electronic address: th.webster@neu.edu.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Webster
authors.affiliation: Department of Pharmaceutics, Jamia Hamdard, Hamdard Nagar, New Delhi, India.
authors.forename: Farhan Jalees
authors.initials: FJ
authors.lastname: Ahmad
mesh_terms: D000279:Administration, Cutaneous; D000666:Amphotericin B / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001228:Aspergillosis / Q000188:drug therapy; D001232:Aspergillus fumigatus / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy; D004655:Emulsions / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D006801:Humans; D051381:Rats; D012867:Skin / Q000187:drug effects / Q000648:ultrastructure; D012869:Skin Absorption
chemical_list: D000935:Antifungal Agents; D004655:Emulsions; D005079:Excipients; D000666:Amphotericin B
keywords: Enhanced flux; Fungal infections; Histopathology; Nanoemulsion; Topical delivery