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Anti-tumor Effect of All-Trans Retinoic Acid Loaded Polymeric Micelles in Solid Tumor Bearing Mice
Authors:Narin Chansri  Shigeru Kawakami  Masayuki Yokoyama  Tatsuhiro Yamamoto  Pensri Charoensit  Mitsuru Hashida
Affiliation:(1) Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan;(2) Kanagawa Academy of Science and Technology, KSP East 404, Sakado 3-2-1, Takatsu-ku, Kawasaki-shi Kanagawa, 213-0012, Japan
Abstract:
Purpose All-trans retinoic acid (ATRA) polymeric micelles were developed for parenteral administration. The distribution characteristics and antitumor activities of ATRA polymeric micelles were evaluated after intravenous administration to mice bearing CT26 solid tumors. Methods ATRA incorporated in poly(ethylene glycol)-poly(benzyl aspartate) block copolymer was prepared by the evaporation method. The levels of [3H]ATRA in blood and tissue including tumor were determined by measuring the radioactivity after injection into mice. The tumor volume and the survival of the mice were determined to assess the anticancer activity. Results The delivery of ATRA by polymeric micelles prolonged the blood circulation and enhanced the accumulation of ATRA in the tumor tissue compared with the administration of free ATRA. Tumor growth was significantly delayed and the survival time of mice was prolonged following the treatment by ATRA polymeric micelles demonstrating the improved anticancer activity of ATRA. Conclusion Polymeric micelles are a promising and effective carrier of ATRA in order to enhance tumor delivery and they have a promising potential application in the treatment of solid tumors.
Keywords:all-trans retinoic acid  antitumor activity  biodistribution  drug targeting  nanomedicine  polymeric micelles
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