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Doxorubicin-incorporated polymeric micelles composed of dextran-b-poly(DL-lactide-co-glycolide) copolymer

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Author(s): Jeong YI | Kim DH | Chung CW | Yoo JJ | Choi KH | Kim CH | Ha SH | Kang DH

Journal: International Journal of Nanomedicine
ISSN 1176-9114

Volume: 2011;
Issue: default;
Start page: 1415;
Date: 2011;
Original page

ABSTRACT
Young-Il Jeong1,*, Do Hyung Kim1,2,*, Chung-Wook Chung1, Jin-Ju Yoo1, Kyung Ha Choi1, Cy Hyun Kim1,2, Seung Hee Ha1, Dae Hwan Kang1,2 1National Research and Development Center for Hepatobiliary Cancer, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea, Research Institute for Convergence of Biomedical Science and Technology, 2School of Medicine, Pusan National University, Yangsan, Republic of Korea*These authors contributed equally to this work.Background: Polymeric micelles using amphiphilic macromolecules are promising vehicles for antitumor targeting. In this study, we prepared anticancer agent-incorporated polymeric micelles using novel block copolymer.Methods: We synthesized a block copolymer composed of dextran and poly (DL-lactide-co-glycolide) (DexbLG) for antitumor drug delivery. Doxorubicin was selected as the anticancer drug, and was incorporated into polymeric micelles by dialysis. Polymeric micelles were observed by transmission electron microscopy to be spherical and smaller than 100 nm, with a narrow size distribution. The particle size of doxorubicin-incorporated polymeric micelles increased with increasing drug content. Higher initial drug feeding also increased the drug content. Results: During the drug-release study, an initial burst release of doxorubicin was observed for 10 hours, and doxorubicin was continuously released over 4 days. To investigate the in vitro anticancer effects of the polymeric micelles, doxorubicin-resistant HuCC-T1 cells were treated with a very high concentration of doxorubicin. In an antiproliferation study, the polymeric micelles showed higher cytotoxicity to doxorubicin-resistant HuCC-T1 cells than free doxorubicin, indicating that the polymeric micelles were effectively engulfed by tumor cells, while free doxorubicin hardly penetrated the tumor cell membrane. On confocal laser scanning microscopy, free doxorubicin expressed very weak fluorescence intensity, while the polymeric micelles expressed strong red fluorescence. Furthermore, in flow cytometric analysis, fluorescence intensity of polymeric micelles was almost twice as high than with free doxorubicin.Conclusion: DexbLG polymeric micelles incorporating doxorubicin are promising vehicles for antitumor drug targeting.Keywords: dextran, polymeric micelle, block copolymer, poly(DL-lactide-co-glycolide)
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