Preparation and characterization of size-controlled polymeric micelle containing cis-dichlorodiammineplatinum(II) in the core.
Polymeric micelles of varying size in the range of 20 to 100 nm entrapping an antitumor drug, cis-dichlorodiammineplatinum(II) (cisplatin, CDDP), were prepared through the polymer-metal complex formation of CDDP with a mixture of poly(ethylene glycol)-poly(alpha,beta-aspartic acid) block copolymer (PEG-P(Asp)) and poly(alpha,beta-aspartic acid) homopolymer (P(Asp)) with the different feed ratio in distilled water. An increased ratio of P(Asp) to PEG-P(Asp) led to an increase in the micellar size in a controllable manner as well as prolongation in the induction period of the micellar decay accompanied by a sustained release of CDDP in physiological saline at 37 degrees C. All of the CDDP-loaded micelles with a different incorporation ratio of P(Asp) exhibited appreciable in vitro cytotoxicity due to CDDP release from the micelles by prolonged incubation. These CDDP-loaded micelles are expected to have potential utility in tumor-directed delivery system of CDDP through the modulated in vivo biodisposition based on the EPR effect.
Nishiyama
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N
Department of Materials Science, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Kataoka
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K
D000465:Algorithms; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D002945:Cisplatin / Q000008:administration & dosage* / Q000737:chemistry; D003520:Cyclophosphamide / Q000031:analogs & derivatives*; D005079:Excipients; D008027:Light; D008823:Micelles; D010455:Peptides; D011092:Polyethylene Glycols; D011108:Polymers; D012542:Scattering, Radiation; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D005079:Excipients; D008823:Micelles; D010455:Peptides; D011108:Polymers; C017645:polyaspartate; D011092:Polyethylene Glycols; C028136:4-S-(propionic acid)sulfidocyclophosphamide; D003520:Cyclophosphamide; D002945:Cisplatin