共载双硫仑与阿霉素纳米胶束的制备和体外评价

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Abstract Objective: To prepare the nano-scal polymer micelles simultaneously encapsulating disulfiram (DSF) and doxorubicin (DOX) and to evaluate its physical and chemical properties in vitro and the ability to reverse the multi-drugs resistance of breast cancer cells against doxorubicin. Methods: Using monomethoxy (polyethylene glycol)-b-P (D, L-lactic-co-glycolic acid)-b-P (L-glutamic acid) (mPEG-PLGA-PGA) as materials, the dual-drugs loaded polymer micelles (DSFDOX-NPs) was prepared by dialysis method and its physical and chemical properties were studied by dynamic light scattering (DLS), transmission electron microscope (TEM). Drug loading content (DLC) and drug loading efficiency (DLE) were measured by HPLC. Furthermore, in vitro drug release profiles from DSFDOX-NPs were explored by dynamic dialysis method. Finally, the cellular toxicity against MCF-7/ADR and the cellular uptake of DSFDOX-NPs were evaluated. Results: DSFDOX-NPs had a mean diameter of (107.5±0.2) nm, and Zeta potential of (-13.7±0.1) mV, determined by DLS. TEM image showed that DSFDOX-NPs had spherical shape, and dry mean diameter of 95 nm. DLC and DLE of disulfiram was 1.91% and 80.30% respectively, while DLC and DLE of doxorubicin was 2.28% and 96.2% respectively. The sustained-release of both of DSF and DOX from DSFDOX-NPs was observed, exhibiting a cascade release profiles with the faster release of DSF followed by a slower release of DOX. DSFDOX-NPs can enhance the cellular uptake of DOX by drug-resistant MCF-7/ADR cells through inhibition of P-gP, displaying the significantly higher cytotoxicity against MCF-7/ADR than DOX solution. Conclusion: DSF and DOX is efficiently encapsulated in DSFDOX-NPs with a particle size of less than 100 nm. The sustained-release of DSF and DOX from DSFDOX-NPs is also observed. More importantly, DSFDOX-NPs displayed multidrugresistance reversal effect on MCF-7/ADR cell.

Key words： disulfiram doxorubicin block copolymer micelles polyglutamicacid polylactic-co-glycolic acid breast neoplasms multi-drugs resistanc

Received: 05 August 2017

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	Xu Xiafang
	Tong Mengqi
	Jiang Qianyao
	Zhao Yingzheng
	Xu Helin.

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https://xb.wmu.edu.cn/EN/ OR https://xb.wmu.edu.cn/EN/Y2018/V48/I2/79

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