Synthesis and antitumor activity of doxorubicin conjugated stearic acid-g-chitosan oligosaccharide polymeric micelles.
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.
Hu
Fu-Qiang
FQ
College of Pharmaceutical Science, Zhejiang University, 388 Yuhangtang Road, Hangzhou 310058, PR China.
Liu
Li-Na
LN
Du
Yong-Zhong
YZ
Yuan
Hong
H
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry; D045744:Cell Line, Tumor / Q000187:drug effects*; D048271:Chitosan / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D008422:Materials Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D018625:Microscopy, Atomic Force; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D009844:Oligosaccharides / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D013229:Stearic Acids / Q000737:chemistry*
D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D008823:Micelles; D009844:Oligosaccharides; D011108:Polymers; D013229:Stearic Acids; C031183:stearic acid; D004317:Doxorubicin; D048271:Chitosan