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  • Title: Synthesis and antitumor activity of doxorubicin conjugated stearic acid-g-chitosan oligosaccharide polymeric micelles.
    Author: Hu FQ, Liu LN, Du YZ, Yuan H.
    Journal: Biomaterials; 2009 Dec; 30(36):6955-63. PubMed ID: 19782395.
    Abstract:
    Doxorubicin conjugated stearic acid-g-chitosan oligosaccharide polymeric micelles (DOX-CSO-SA) was synthesized via cis-aconityl bond between the anticancer drug doxorubicin (DOX) and stearic acid grafted chitosan oligosaccharide (CSO-SA) in this paper. The CSO-SA micelles had been demonstrated faster internalization ability into tumor cells. Here, the CSO-SA with 6.47% amino substituted degree (SD%) was used to synthesize DOX-CSO-SA. The critical micelle concentration (CMC) was about 0.14 mg mL(-1). The micelles with 1 mg mL(-1) CSO-SA concentration had 32.7 nm number average diameter with a narrow size distribution and 51.5 mV surface potential. After conjugating with doxorubicin, CMC of DOX-CSO-SA descended; the micellar size increased; and the zeta potential decreased. The DOX-CSO-SA micelles indicated pH-dependent DOX release behavior. The release rate of DOX from DOX-CSO-SA micelles increased significantly with the reductions of the pH for release medium from 7.2 to 5.0. In vitro antitumor activity tests of DOX-CSO-SA micelles against human breast carcinoma (MCF-7) cells and their multi-drug resistant (MCF-7/Adr) cells presented the reversal activity against DOX resistance MCF-7 cells (MCF-7/Adr). The in vivo antitumor activity results showed that DOX-CSO-SA micelles treatments effectively suppressed the tumor growth and reduced the toxicity against animal body than commercial doxorubicin hydrochloride injection.
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