基于羟乙基淀粉-姜黄素前药的SN38协同给药胶束构建与评价OA北大核心CSTPCD

Synergetic chemotherapy can inhibit cancer cell proliferation via various metabolic pathways,which demonstrates superiorities in improving therapeutic efficacy and avoiding multidrug resistance.In this work,synergetic therapeutic micelles based on quaternary ammonium salt substituted hydroxyethyl starch-curcumin(QHES-S-CUR)conjugates were constructed to encapsulate 7-ethyl-10-hydroxycamptothecin(SN38).Stability of curcumin/SN38 mixture was assessed by molecular dynamics simulation.Then,synergetic therapeutic micelles loading with SN38 were prepared by nanoprecipitation.Effects of QHES-S-CUR/SN38 weight ratios on morphologies and size distributions of SN38@QHES-S-CUR were investigated in detail.At a weight ratio of 20:1,spherical nanoparticles with an average size of(258.76±28.76)nm could be obtained.In vitro drug release profiles indicated that curcumin and SN38 were released under the trigger of simulated tumor microenvironment.In addition,SN38@QHES-S-CUR exhibited more effective cytotoxicity to CT-26 cells than SN38 alone.This work expands the application of amphiphilic prodrugs to the delivery of hydrophobic chemotherapy drugs,which provides a new sight of synergetic chemotherapy.