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Characterization of physical entrapment and chemical conjugation of adriamycin in polymeric micelles and their design for in vivo delivery to a solid tumor |
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| Authors: | Masayuki Yokoyama Shigeto Fukushima Ryuji Uehara Kazuya Okamoto Kazunori Kataoka Yasuhisa Sakurai Teruo Okano |
| Institution: | a Institute of Biomedical Engineering, Tokyo Women's Medical College, Kawada-cho, 8-1, Shinjuku-ku, Tokyo 162, Japan b Nippon Kayaku Co. Ltd., Iwahana 219, Takasaki-shi, Gunma 370-12, Japan c Department of Materials Science and Technology, Faculty of Industrial Science and Technology, Science University of Tokyo, Yamazaki 2641, Noda-shi, Chiba 278, Japan d International Center for Biomaterials Science (ICBS), in Research Institute for Biosciences, Science University of Tokyo, Yamazaki 2669, Noda-shi, Chiba 278, Japan |
| Abstract: | An anticancer drug adriamycin (ADR) was incorporated into polymeric micelles forming from poly(ethylene glycol)-poly(aspartic acid) block copolymer by chemical conjugation and physical entrapment. Structural stability of the polymeric micelles was found to be dependent on both the contents of chemically conjugated and physically entrapped ADR. The polymeric micelle with high contents of the chemically conjugated ADR and the physically entrapped ADR expressed very high in vivo antitumor activity against murine C 26 tumor, while the polymeric micelle with only the chemically conjugated ADR showed negligible in vivo activity. This indicates that the physically entrapped ADR played a major role in antitumor activity in vivo. For the polymeric micelle with the high ADR contents, it was found that a dimer of adriamycin molecules formed and that this dimer was physically entrapped in the inner core of the micelle as well as intact ADR. |
| Keywords: | Polymeric micelles Stability Anticancer drug Adriamycin Dimer |
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