title: Skin targeted lipid vesicles as novel nano-carrier of ketoconazole: characterization, in vitro and in vivo evaluation.
abstract: Liposomal carriers for topical drug delivery have been studied since the 1980s and have evoked a considerable interest. However, the conventional liposomes do not deeply penetrate into the skin and remain confined to the outer layer of SC. In order to increase skin targeting of ketoconazole (KCZ), a hydrophobic broad-spectrum antifungal agent, this study describes novel lipid vesicles as nano-carriers for topical delivery. In this paper, lipid vesicular systems including conventional liposomes (CL), ethosomes, deformable liposomes (DL) and ethanol-containing deformable liposomes (DEL) were prepared as nano-carriers for KCZ, respectively. Sodium dodecyl sulfate [SDS, 0.08 % (W/V)] was used as edge activator for DL and DEL preparation. Characterization of the vesicles was based on particle size, zeta potential, entrapment efficiency and transmission electron microscopy (TEM). In addition, in vitro permeation profile was obtained using vertical diffusion Franz cells by porcine skin. The in vivo accumulation of KCZ was also evaluated in rat skin. Confocal microscopy was performed to visualize the penetration of fluorescently labeled vesicles into skin. All of the lipid vesicles showed almost spherical structures with low polydispersity index (PDI < 0.3) and nano-metric size (no more than 160 nm). The results demonstrated that DEL dramatically improved both in vitro and in vivo skin deposition compared to the CLs (P < 0.05), which was further confirmed by confocal laser scanning microscopy study. In vivo pharmacodynamic studies showed DEL improved antifungal activity against Candida albicans in shorter duration of time. Therefore, based on present study, the novel nano-carrier DEL capable of enhancing skin target effect and forming a micro drug-depot could serve as an effective skin targeting delivery for KCZ as an anti-fungal agent in local therapy.
authors.affiliation: Tianjin Key Laboratory of Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Guo
authors.forename: Jinping
authors.initials: J
authors.lastname: Wang
authors.forename: Man
authors.initials: M
authors.lastname: Ma
authors.forename: Fengping
authors.initials: F
authors.lastname: Tan
authors.forename: Nan
authors.initials: N
authors.lastname: Li
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage; D004058:Diffusion; D066298:In Vitro Techniques; D007654:Ketoconazole / Q000008:administration & dosage* / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry*; D051381:Rats; D012867:Skin / Q000737:chemistry*; D012869:Skin Absorption / Q000502:physiology*; D013207:Staphylococcal Skin Infections / Q000188:drug therapy* / Q000473:pathology; D013552:Swine; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D008081:Liposomes; D053769:Nanocapsules; D007654:Ketoconazole
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