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Stability of micellar structures in the presence of rabbit serum of adriamycin-conjugated poly (ethylene oxide)-poly(aspartic acid) block copolymers with several compositions was evaluated by gel-permeation chromatography. It was revealed that these adriamycin-block copolymer conjugates with the longer poly (ethylene oxide) chains and the shorter adriamycin-conjugated poly (aspartic acid) chains showed the more stable micelle formation. Physically trapped adriamycin in the inner core of the micelles was observed to influence on the stability. Furthermore, the stability of the micellar structures was found to well correlate with in vivo antitumor activity of the conjugates. These results present a strategy and a methodology in designing antitumor drug-block copolymer conjugates for highly selective delivery to tumors.

Micelle-forming block copolymer–drug conjugates, Adriamycin-conjugated polyethylene glycol–poly(aspartic acid) block copolymers (PEG-P[Asp(ADR)]), were synthesized in eight compositions with varying chain lengths of the segments constituting the block co-polymer. The antitumor activity of this micelle-forming polymeric anticancer drug against murine colon adenocarcinoma 26 (C 26) was evaluated by injection into the tail vein. The in vivo activity of the micelle-forming polymeric anticancer drug was revealed to be strongly dependent on the composition, while the in vitro cytotoxic activity was found to be in the same range regard-less of the composition. One composition of PEG–P[Asp(ADR)] was observed to significantly suppress tumor growth and to prolong survival of the treated mice in a wide dose range. These results indicated that selective delivery of the micelle-forming polymeric anti-cancer drug to the tumor was achieved by the appropriate composition of the block copolymer–drug conjugates.

Adriamycin, a hydrophobic anticancer drug, was conjugated with poly(ethylene oxide)-poly(aspartic acid) block copolymers composed of various lengths of each block copolymer segment ranging from 1000 to 12,000 in molecular weight and from 10 to 80 units, respectively. Conjugation was achieved without precipitation by adjusting the ratio of adriamycin to aspartic acid residues of the block copolymer and the quantity of DMF used for the reaction. Thus obtained conjugates showed high water solubility irrespective of a large amount of the conjugated adriamycin. Furthermore, these conjugates were found to form micellar structures with a hydrophobic inner core and a hydrophilic outer shell. This micellar architecture may be utilized for effective drug targeting.