title: Development of amphotericin B-loaded cubosomes through the SolEmuls technology for enhancing the oral bioavailability.
abstract: The oral administration of amphotericin B (AmB) has the major drawback of poor bioavailability. The aim of this work was to evaluate the potential of AmB-loaded cubosomes as an oral formulation with improved bioavailability. This manuscript firstly developed AmB-loaded cubosomes by using the SolEmuls technology. The encapsulation efficiency, the in vitro release, and stability studies in simulated gastrointestinal fluid were used to evaluate AmB-loaded cubosomes. The acute nephrotoxicity, bioavailability, and tissue distribution study of AmB-loaded cubosomes were assayed upon oral administration to rats. SAXS and cryo-TEM exhibited AmB-loaded cubosomes as a bicontinuous cubic liquid crystalline phase with Pn3m geometry. The encapsulation efficiency and the results of in vitro release and stability studies in simulated gastrointestinal fluid further demonstrated that AmB was successfully encapsulated in cubosomes. AmB-loaded cubosomal formulation orally administrated in rats did not show nephrotoxicity and its relative bioavailability was approximately 285% as compared to Fungizone®. The AmB-loaded cubosomal formulation presented an effective potential approach for enhancing the oral bioavailability of AmB.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China.
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Yang
authors.forename: Yinhe
authors.initials: Y
authors.lastname: Tan
authors.forename: Meiwan
authors.initials: M
authors.lastname: Chen
authors.forename: Linghui
authors.initials: L
authors.lastname: Dian
authors.forename: Ziyun
authors.initials: Z
authors.lastname: Shan
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Peng
authors.forename: Chuanbin
authors.initials: C
authors.lastname: Wu
mesh_terms: D000284:Administration, Oral; D000666:Amphotericin B / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004355:Drug Stability; D050866:Liquid Crystals / Q000737:chemistry; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D000900:Anti-Bacterial Agents; D000666:Amphotericin B