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Toxicity and Antitumor Activity against Solid Tumors of Micelle-forming Polymeric Anticancer Drug and Its Extremely Long Circulation in Blood

Institute of Biomedical Engineering, Tokyo Women's Medical College; Kawada-cho, Shinjuku-ku, Tokyo 162 [M. Y., T. O., Y. S.] Nippon Kayaku Co., Ltd., Shimo 3-31-12, Kita-ku, Tokyo 115 [H. E., C. S.]; and Department of Materials Science and Technology and Research Institute for Biosciences, Science University of Tokyo, Yamazaki 2641, Noda-shi, Chiba 278 [K. K.], Japan

Toxicity and in vivo antitumor activity against five solid tumors (C 26, C 38, M 5076, MKN-45, MX-1) of Adriamycin (ADR)-conjugated poly(ethylene glycol)-poly(aspartic acid) block copolymer {PEG-P[Asp(ADR)]} were evaluated, and its pharmacokinetic behavior in blood and biodistribution by i.v. injection were obtained. PEG-P[Asp(ADR)] was revealed to express higher antitumor activity than ADR against all the examined tumors except MKN-45. Especially against C 26, PEG-P[Asp(ADR)] expressed critical suppression of tumor growth and considerably prolonged life span of the treated mice. PEG-P[Asp(ADR)] was observed in blood at much higher concentrations with a longer half-life than ADR after the i.v. injection. PEG-P[Asp(ADR)] was known to form a micellar structure with a diameter of approximately 50 nm and a narrow distribution in phosphate-buffered saline. Therefore, the stabilized circulation of ADR residue in blood by binding to the block copolymer was considered to result from the micellar structure which possesses the hydrated outer shell composed of the poly(ethylene glycol) chains.

¹ To whom requests for reprints should be addressed.

Received 12/26/90. Accepted 3/28/91.

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