Biodistribution characteristics of all-trans retinoic acid incorporated in liposomes and polymeric micelles following intravenous administration.
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.
Kawakami
Shigeru
S
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
Opanasopit
Praneet
P
Yokoyama
Masayuki
M
Chansri
Narin
N
Yamamoto
Tatsuhiro
T
Okano
Teruo
T
Yamashita
Fumiyoshi
F
Hashida
Mitsuru
M
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*
D001593:Benzyl Compounds; D008081:Liposomes; D008823:Micelles; C493635:polyethylene glycol-block-polyaspartic acid; D011092:Polyethylene Glycols; D014212:Tretinoin