title: Evaluating the potential of cubosomal nanoparticles for oral delivery of amphotericin B in treating fungal infection.
abstract: The oral administration of amphotericin B (AmB) has a major drawback of poor bioavailability. The aim of this study was to investigate the potential of glyceryl monoolein (GMO) cubosomes as lipid nanocarriers to improve the oral efficacy of AmB. Antifungal efficacy was determined in vivo in rats after oral administration, to investigate its therapeutic use. The human colon adenocarcinoma cell line (Caco-2) was used in vitro to evaluate transport across a model of the intestinal barrier. In vivo antifungal results showed that AmB, loaded in GMO cubosomes, could significantly enhance oral efficacy, compared against Fungizone, and that during a 2 day course of dosage 10 mg/kg the drug reached effective therapeutic concentrations in renal tissue for treating fungal infections. In the Caco-2 transport studies, GMO cubosomes resulted in a significantly larger amount of AmB being transported into Caco-2 cells, via both clathrin- and caveolae-mediated endocytosis, but not macropinocytosis. These results suggest that GMO cubosomes, as lipid nanovectors, could facilitate the oral delivery of AmB.
authors.affiliation: Department of Pharmacy, Songjiang Hospital Affiliated The First People's Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China ; Shanghai Songjiang Hospital Affiliated Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People's Republic of China.
authors.forename: Meiwan
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Songjiang Hospital Affiliated The First People's Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Muhua
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Songjiang Hospital Affiliated The First People's Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Songjiang Hospital Affiliated The First People's Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Fang
authors.affiliation: Department of Pharmacy, Songjiang Hospital Affiliated The First People's Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
mesh_terms: D000284:Administration, Oral; D000666:Amphotericin B / Q000008:administration & dosage* / Q000737:chemistry*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry; D018938:Caco-2 Cells; D002177:Candidiasis / Q000188:drug therapy* / Q000473:pathology; D005240:Feasibility Studies; D006801:Humans; D008297:Male; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D053769:Nanocapsules; D000666:Amphotericin B
keywords: absorption mechanism; amphotericin B; antifungal activity; glyceryl monoolein cubosomes; oral delivery