Optimization of Drug Loading Process of Paclitaxel Exosomes and Its Anti-tumor Study in Vitro
Objective To refine the drug-loading process of the paclitaxel exosome delivery system and evaluate its efficacy and safety,thereby furnishing a foundation for the development of novel anti-liver cancer formulations. Methods Bone marrow mesenchymal stem cell-derived exosomes (BMSCs-Exo) were extracted using the ultracentrifugation method. Paclitaxel (PTX) was encapsulated into the exosomes via electroporation,with drug encapsulation efficiency serving as the evaluation criterion. The drug loading process was optimized through response surface method. High performance liquid chromatography was applied to determine the drug loading capacity of paclitaxel-loaded exosomes(Exo-PTX)and investigate the drug release behavior. The inhibitory effect of Exo-PTX on the proliferation of HepG2 was examined using the CCK-8 assay. Additionally,hemolysis test was used to evaluate the safety of Exo-PTX. Results The optimal conditions for drug loading via electroporation for Exo-PTX were as follows:PTX drug concentration of 81.80 μg·mL-1,voltage of 0.6 mV,and number of pulses of eight. The average encapsulation efficiency of Exo-PTX was (22.38±0.08)％. Meanwhile,Exo-PTX demonstrated excellent sustained-release properties and accelerated release in the slightly acidic tumor microenvironment. The cumulative release rates at 48 h in simulated body fluid and tumor environments were (49.35±0.67)％ and (61.94±0.43)％ at 48 h,respectively. Exo-PTX showed significant inhibitory effects on HepG2 cells in vitro and revealed no risk of hemolysis. Conclusion Exo-PTX,which was prepared under optimal loading conditions,exhibited robust in vitro anti-liver cancer effects in a dose-dependent. Moreover,Exo-PTX showed excellent sustained-release properties. The study provides a basis for the secondary development of PTX formulations.
Response surface methodexosomes derived from bone marrow mesenchymal stem cellselectroporation methodpaclitaxelant-itumor
万方数据
维普
