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Block Copolymer Design for Camptothecin Incorporation into Polymeric Micelles for Passive Tumor Targeting

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Abstract

Purpose. Polymeric micelles were designed for targeting of a water-insoluble anticancer agent, camptothecin (CPT). Chemical structures of inner core segment were optimized to achieve high incorporation efficiency and stable CPT-loaded micelles.

Methods. Poly(ethylene glycol)-poly(β-benzyl L-aspartate) block copolymer (PEG-PBLA) was synthesized. The PBLA chain was modified by alkaline hydrolysis of its benzyl group followed by esterification with benzyl, n-butyl, and lauryl groups. Incorporation of CPT into micelles was carried out by an evaporation method. The stability of drug-loaded micelles was studied by gel-permeation chromatography (GPC), and their in vitro release behaviors were analyzed.

Results. CPT was incorporated into polymeric micelles constructed by various block copolymers. Among the esterified groups, block copolymers with high benzyl ester contents showed high CPT loading efficiency and stable CPT-loaded micelles. In chain lengths, 5-27 Bz-69 showed the highest incorporation efficiency. In contrast, 5-52 Bz-67, which had a longer hydrophobic chain, showed low incorporation efficiency. Release of CPT from the micelles was dependent on the benzyl contents and chain lengths. Sustained release was obtained when the benzyl content was high.

Conclusions. CPT was successfully incorporated into polymeric micelles with high efficiency and stability by optimizing chemical structures of the inner core segment.

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Authors and Affiliations

  1. Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Kawada-cho 8-1, Shinjuku-ku, Tokyo, 162-8666, Japan

    Praneet Opanasopit & Teruo Okano

  2. Kanagawa Academy of Science and Technology, KSP Buld. East 404, Sakado 3-2-1, Takatsu-ku, Kawasaki-shi, Kanagaka-ken, 213-0012, Japan

    Masayuki Yokoyama

  3. Institute of Medical Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo, 142-8501, Japan

    Masato Watanabe, Kumi Kawano & Yoshie Maitani

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  1. Praneet Opanasopit
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  2. Masayuki Yokoyama
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Opanasopit, P., Yokoyama, M., Watanabe, M. et al. Block Copolymer Design for Camptothecin Incorporation into Polymeric Micelles for Passive Tumor Targeting. Pharm Res 21, 2001–2008 (2004). https://doi.org/10.1023/B:PHAM.0000048190.53439.eb

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