Formulation and Evaluation of Paclitaxel-Loaded Polymeric Nanoparticles Composed of Polyethylene Glycol and Polylactic Acid Block Copolymer

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概要

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• To develop potent paclitaxel (PTX) formulations for cancer chemotherapy, we formulated PTX into polymeric nanoparticles composed of polyethylene glycol (PEG) and polylactic acid (PLA) block copolymer (PN-PTX). First, the physicochemical properties of PN-PTX prepared were assessed; the mean particle size was around 80 nm and the zeta potential was found to be almost neutral. Next, the in vitro PTX release property was assessed by a dialysis method. Although rapid release of PTX was observed just after dosing, around 70% of PTX was stably incorporated in polymeric nanoparticles for a long time in the presence of serum. Then, the in vivo pharmacokinetics of PN-PTX after intravenous administration was investigated in Colon-26 (C26) tumor-bearing mice. Both polymeric nanoparticles and PTX incorporated exhibited a long blood circulating property, leading to enhanced permeability and retention (EPR) effect-driven, time-dependent tumor disposition of PTX. Tumor distribution increased gradually for 24 h, and tissue uptake clearance of polymeric nanoparticles in the liver and spleen was lower than that of PEG liposomes. Since these results indicated that the in vivo disposition characteristics of PN-PTX were very favorable, we then evaluated the anti-tumor effect of PN-PTX in C26 tumor-bearing mice. However, PN-PTX did not exhibit any significant anti-tumor effect, presumably due to the poor PTX release from polymeric nanoparticles. From these results, it is considered that the favorable pharmacokinetic properties of nanoparticles and the drug incorporated do not always lead to its potent in vivo pharmacological activity, suggesting the importance of PTX release properties within tumor tissues.

• 公益社団法人　日本薬学会の論文

著者

• KONO Yusuke

  Division of Earth Rotation, National Astronomical Observatory

• Ono Tsutomu

  Department Of Chemical Engineering Faculty Of Engineering Kyushu University

• Ogawara Ken-ichi

  Department Of Pharmaceutics Faculty Of Pharmaceutical Sciences Okayama University

• Ogawara Ken-ichi

  Division Of Pharmaceutical Sciences Graduate School Of Medicine Dentistry And Pharmaceutical Science

• Higaki Kazutaka

  Division Of Pharmaceutical Sciences Graduate School Of Medicine Dentistry And Pharmaceutical Science

• Araki Tomoya

  Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University

• Watanabe Takaichi

  Department of Material and Energy Science, Graduate School of Environmental Science, Okayama University

• Kimura Toshikiro

  Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University

• Kono Yusuke

  Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University

• Ono Tsutomu

  Department of Material and Energy Science, Graduate School of Environmental Science, Okayama University

• Higaki Kazutaka

  Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University

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