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Biodistribution of Micelle-Forming Polymer–Drug Conjugates

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Abstract

Polymeric micelles have potential utility as drug carriers. To this end, polymeric micelles based on AB block copolymers of polyethylene oxide (PEG) and poly(aspartic acid) [p(Asp)] with covalently bound Adriamycin (ADR) were prepared. The micelle forming polymer–drug conjugates [PEO-p(Asp(ADR)] were radiolabeled and their biodistribution was investigated after intravenous injection in mice. Long circulation times in blood for some compositions of PEO-p[Asp(ADR)] conjugates were evident, which are usually atypical of colloidal drug carriers. This was attributed to the low interaction of the PEO corona region of the micelles with biocomponents (e.g., proteins, cells). Low uptake of the PEO-p(Asp(ADR)] conjugates in the liver and spleen was determined. The biodistribution of the PEO-p[Asp(ADR)] conjugates was apparently dependent on micelle stability; stable micelles could maintain circulation in blood, while unstable micelles readily formed free polymer chains which rapidly underwent renal excretion. Long circulation times in blood of PEO-p(Asp(ADR)] conjugates are thought to be prerequisite for enhanced uptake at target sites (e.g., tumors).

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Authors and Affiliations

  1. International Center for Biomaterials Science, Research Institute for Bioscience, Science University of Tokyo, Yamazaki 2669, Noda-shi, Chiba, 278, Japan

    Glen S. Kwon, Masayuki Yokoyama, Teruo Okano, Yasuhisa Sakurai & Kazunori Kataoka

  2. Institute of Biomedical Engineering, Tokyo Women's Medical College, Kawada-cho, Shinjuku-ku, Tokyo, 162, Japan

    Glen S. Kwon, Masayuki Yokoyama, Teruo Okano & Yasuhisa Sakurai

  3. Department of Materials Science and Technology and Research Institute for Bioscience, Science University of Tokyo, Yamazaki 2641, Noda-shi, Chiba, 278, Japan

    Kazunori Kataoka

Authors
  1. Glen S. Kwon
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  2. Masayuki Yokoyama
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  3. Teruo Okano
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  4. Yasuhisa Sakurai
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  5. Kazunori Kataoka
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Kwon, G.S., Yokoyama, M., Okano, T. et al. Biodistribution of Micelle-Forming Polymer–Drug Conjugates. Pharm Res 10, 970–974 (1993). https://doi.org/10.1023/A:1018998203127

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  • DOI: https://doi.org/10.1023/A:1018998203127

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