title: Physical characterization and in vivo pharmacokinetic study of self-assembling amphotericin B-loaded lecithin-based mixed polymeric micelles.
abstract: To alleviate the inherent problems of amphotericin B (AmB), such as poor water solubility and nephrotoxicity, a novel self-assembling mixed polymeric micelle delivery system based on lecithin and combined with amphiphilic polymers, Pluronic(®), Kolliphor(®), d-alpha tocopheryl polyethylene glycol succinate, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(poly(ethylene glycol)-2000 (DSPE-PEG2K) was developed. An optimal formulation (Ambicelles) composed of AmB:lecithin:DSPE-PEG2K in a 1:1:10 weight ratio was obtained. The particle size, polydispersion index, drug encapsulation efficiency, and drug loading were 187.20±10.55 nm, 0.51±0.017, 90.14%, and 7.51%, respectively, and the solubility was increased from 0.001 to 5 mg/mL. Compared with that of Fungizone(®), the bioavailability of Ambicelles administered intravenously and orally increased 2.18- and 1.50-fold, respectively. Regarding the in vitro cytotoxicity, Ambicelles had a higher cell viability than free AmB solution or Fungizone(®) did. With pretreatment of 50 μg/mL ethanolic extract of Taiwanofungus camphoratus followed by AmB to HT29 colon cancer cells, the 50% inhibitory concentration of AmB solution was 12 μg/mL, whereas that of Ambicelles was 1 μg/mL, indicating that Ambicelles exerted a greater synergistic anticancer effect.
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ying-Chen
authors.initials: YC
authors.lastname: Chen
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Su
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Hua-Jun
authors.initials: HJ
authors.lastname: Jhan
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Hsiu-O
authors.initials: HO
authors.lastname: Ho
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ming-Thau
authors.initials: MT
authors.lastname: Sheu
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000666:Amphotericin B / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D001682:Biological Availability; D019073:HT29 Cells; D006801:Humans; D054709:Lecithins / Q000737:chemistry*; D008297:Male; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013997:Time Factors; D014810:Vitamin E / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D054709:Lecithins; D008823:Micelles; D010714:Phosphatidylethanolamines; D011108:Polymers; D014810:Vitamin E; D011092:Polyethylene Glycols; D000666:Amphotericin B; C014225:tocophersolan
keywords: DSPE-PEG; amphiphilic polymer; amphotericin B; lecithin; micelle