mPEG-PDLLA&mPEG-DSPE载奥沙利铂复合胶束的制备及性能评价OA北大核心CSTPCD

Objective:To address the challenges associated with the low encapsulation efficiency of water-soluble drugs,poor stability and negligible endocytosis in micelles.Method:mPEG-DSPE and mPEG-PDLLA were used as carrier materials and ox-aliplatin as model drug to prepare mPEG-DSPE&mPEG-PDLLA/OXA mixed NPs by flash nanoprecipitation.The performances of mixed NPs were compared with mPEG-PDLLA/OXA NPs and LPHNP/OXA NPs.Results:The optimal preparation process of mixed NPs obtained by single factor screening was as follows:the total flow rate was 4 mL/min with a flow rate ratio of 1∶3,the total material concentration was 3.75 mg/mLwith a material ratio was 1∶2,and the anti-solvent was acetonitrile.The three kinds of NPs had uniform particle sizes and all of their encapsulation efficiencies were more than 70%.The in vitro drug release test showed that the release rate of the mixed micelles which could be completely released was slower than that of the ordinary mi-celles.The results of uptake and apoptosis assay showed that the mixed micelles had the best uptake performance and cytotoxicity efficacy among the three NPs.Conclusions:The preparation of mixed micelles by flash nanoprecipitation which is a simple and con-venient preparation method for commercialization,can achieve high encapsulation of water-soluble drugs.At the same time,the designed mixed micelles mPEG-DSPE&mPEG-PDLLA/OXA exhibits excellent abilities including favorable stability,superior uptake and robust cytotoxicity efficacy.This research provides a new idea for the application and transformation of micelles.