title: Ascorbyl dipalmitate/PEG-lipid nanoparticles as a novel carrier for hydrophobic drugs.
abstract: L-ascorbyl 2,6-dipalmitate (ASC-DP), a fatty ester derivative of ascorbic acid, is poorly soluble in water and does not spontaneously form micelles or liposomal structures in water. In this study, we attempted to prepare an ASC-DP/surfactant nano-sized complex as a carrier for hydrophobic drugs. Samples were prepared by hydrating a solvent-evaporated film of ASC-DP/surfactant at a molar ratio of 1:1. Among the surfactants tested, distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG) was found to form stable nanoparticles with ASC-DP (average particle size: ca. 67 nm). Several hydrophobic drugs were incorporated in the ASC-DP/DSPE-PEG nanoparticles. Stability, toxicity, and blood residence of the drug-containing ASC-DP/DSPE-PEG nanoparticles were evaluated using amphotericin B (AmB) as the model drug. By intravenously administering mice with the formulations, we determined the minimum lethal dose of Fungizone, a formulation of AmB solubilized with sodium deoxycholate, was 3.0 mg/kg, while that of AmB/ASC-DP/DSPE-PEG nanoparticles was 10.0 mg/kg. When 2.0 mg/kg, Fungizone was administered, the mice showed higher renal and hepatic toxicities. Intravenously administered AmB/ASC-DP/DSPE-PEG nanoparticles demonstrated higher concentration in plasma than Fungizone. Thus, the ASC-DP/DSPE-PEG nanoparticle system appears to be a promising delivery system for hydrophobic drugs.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan. moribe@p.chiba-u.ac.jp
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Moribe
authors.forename: Sunao
authors.initials: S
authors.lastname: Maruyama
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Inoue
authors.forename: Toyofumi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fukami
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tomono
authors.forename: Kenjirou
authors.initials: K
authors.lastname: Higashi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tozuka
authors.forename: Keiji
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D001205:Ascorbic Acid / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D051379:Mice; D053758:Nanoparticles; D010168:Palmitates / Q000737:chemistry*; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D018675:Toxicity Tests
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D010168:Palmitates; D010714:Phosphatidylethanolamines; D013501:Surface-Active Agents; C549095:ascorbyl 2,6-dipalmitate; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D000666:Amphotericin B; D001205:Ascorbic Acid