title: Biodistribution characteristics of all-trans retinoic acid incorporated in liposomes and polymeric micelles following intravenous administration.
abstract: The aim of this study was to investigate the biodistribution characteristics of all-trans retinoic acid (ATRA) incorporated in liposomes and polymeric micelles following intravenous administration. [3H] ATRA were incorporated in distearoylphosphatidylcholine (DSPC)/cholesterol (6:4) liposomes. Two types of block copolymers, poly (ethylene glycol)-b-poly-(aspartic acid) derivatives with benzyl (Bz-75) groups, were synthesized to prepare the polymeric micelles for [(3)H]ATRA incorporation. ATRA were dissolved in mouse serum to analyze their inherent distribution. After intravenous administration, the blood concentration of [3H] ATRA in liposomes and polymeric micelles (Bz-75) was higher than that of inherent [3H]ATRA, suggesting that liposomes and polymeric micelles (Bz-75) control the distribution of ATRA. Pharmacokinetic analysis demonstrated that [3H]ATRA incorporated in polymeric micelles (Bz-75) exhibit the largest AUC(blood) and lowest hepatic clearance of ATRA, suggesting that polymeric micelles (Bz-75) are an effective ATRA carrier system for acute promyelocytic leukemia (APL) therapy. These results have potential implications for the design of ATRA carriers for APL patients.
authors.affiliation: Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kawakami
authors.forename: Praneet
authors.initials: P
authors.lastname: Opanasopit
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Narin
authors.initials: N
authors.lastname: Chansri
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Teruo
authors.initials: T
authors.lastname: Okano
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Yamashita
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hashida
mesh_terms: D000818:Animals; D001593:Benzyl Compounds / Q000737:chemistry*; D004339:Drug Compounding; D007275:Injections, Intravenous; D008081:Liposomes; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008823:Micelles; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D014018:Tissue Distribution; D014212:Tretinoin / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry*
chemical_list: D001593:Benzyl Compounds; D008081:Liposomes; D008823:Micelles; C493635:polyethylene glycol-block-polyaspartic acid; D011092:Polyethylene Glycols; D014212:Tretinoin