Yokoyama Masayuki

Block copolymer micelles as vehicles for drug delivery

Abstract There is a wide-spread consensus that characteristics of drug vehicles determine the applicability of the site-specific delivery of drugs. This article focused on the promising features of block copolymer micelles as drug vehicles mimicking the natural carrier-systems with supramolecular structures (i.e. viruses and lipoproteins). Considerable discussions are made on the physicochemical characteristics of polymeric micelles in aqueous milieu with shedding light on earlier works done in the field. Advantageous features of polymeric micelles as drug vehicles are summarized as: (1) formation of environmentally-separated microcontainer of drugs through supramolecular assemblage, (2) installation of anchoring moiety on the surface, (3) duration in the biological compartment and (4) programmable chronological stability. Then, our recent work concerning polymeric micelles with anti-tumor activity is presented to demonstrate these advantageous features of polymeric micelles. Worth noticing is that higher anti-tumor activity was achieved by adriamycin-conjugated micelles compared with parental adriamycin, indicating that a considerable improvement in cancer chemotherapy is feasible by the use of appropriate vehicle systems.

Polymer micelles as novel drug carrier: Adriamycin-conjugated poly(ethylene glycol)-poly(aspartic acid) block copolymer

Abstract A micelle-forming polymeric drug was synthesized using adriamycin (an anti-cancer drug) and poly(ethylene glycol)-poly(aspartic acid) block copolymers. The micelle had a narrow and unimodal size distribution, and its diameter was observed to be ca. 50 nm, the range corresponding to viruses. This micelle-forming polymeric drug exhibited good water solubility and good stability against precipitation irrespective of the large quantity of incorporated hydrophobie adriamycin. In vivo anti-cancer activity of this polymeric drug against P-388 mouse leukemia was studied by changing the length of the poly(aspartic acid) chain of the block copolymer. The polymeric drug showed excellent in vivo anti-cancer activity, judged from the ratio of the survival period of the treated mice to that of the control (T/C), with lower toxicity than that of adriamycin. These results point to a promising figure of polymeric micelles as novel drug carriers.

Influencing factors on in vitro micelle stability of adriamycin-block copolymer conjugates

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.