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| Gambogic acid-encapsulated polymeric micelles improved therapeutic effects on pancreatic cancer |
| Yan Wanga, Xinxin Wanga, Jing Zhanga, Li Wanga, Chunqing Oua, Yaqian Shua, Qinjie Wua, Guolin Mab, Changyang Gonga |
a State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China;
b Department of Radiology, China-Japan Friend Hospital, Beijing 100029, China |
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| Guide Monomethyl poly(ethylene glycol)-poly(ε-caprolactone)-poly(trimethylene carbonate) (MPEG-P(CL-ran-TMC)) copolymer was synthesized, which could encapsulate GA by a single-step solid dispersion and form nano-sized micelles. The MPEG-P(CL-ran-TMC) based nano-formulation of GA could improve the anti-tumor effect in vivo, which may serve as a candidate for pancreatic cancer therapy. |
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Abstract Gambogic acid(GA) is a natural product with potent anticancer activity in vitro.However,poorwatersolubility and systematic toxicity limit the further clinical application of GA. Micellization of hydrophobic molecule could effectively ameliorate aqueous dispersity of GA and induce better blood retention and tumor accumulation, hence lead to improved stability and therapeutic effect of GA. In this study, monomethyl poly(ethylene glycol)-poly(ε-caprolactone)-poly(trimethylene carbonate) (MPEG-P(CL-ran-TMC)) was used to encapsulate GA by a single-step solid dispersion method to form a GA encapsulated MPEG-P(CL-ran-TMC) micelles (GA micelles). GA micelles were characterized with a small particle size (44 ±1 nm), high drug loading content(26.28% ± 0.12%) and high-effici encyencapsulation (87.59% ± 0.41%). Compared with free GA, GA micelles showed better dispersion in water, prolonged release behavior in vitro, and enhanced tumor cellular uptake. GA micelles could also effectively induce apoptosis in AsPC-1 cells. Compared with free GA, GA micelles exhibited superior antitumor efficacy and better apoptosis induced effect in a subcutaneous xenograft mouse model of AsPC-1 cells. In conclusion, GA micelles which showed high-efficiency anti-tumor effect in vitro and in vivo may serve as a candidate for pancreatic cancer therapy.
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Received: 06 January 2019
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| Fund:This work was financially supported by National Natural Science Foundation of China (No. 81822025), National Program for Support of Top-notch Young Professionals (No. W02070141) and 1 3 5 Project for Disciplines of Excellence, West China Hospital, Sichuan University. |
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