Preparation and Characterization of Targeted Micelles Co-Loaded with Sorafenib and Disulfiram
Objective To prepare Pluronic P123-galactose(sorafenib/disulfiram-galactose-P123)micelles co-loaded with sorafenib and disulfiram.Methods CCK-8 method was used to select the optimal drug synergistic ratio of sorafenib and disulfiram.Sorafenib/disulfiram-galactose-P123 micelles were prepared by the thin film hydration method,and the optimal process was optimized by the central composite design-response surface methodology(CCD-RSM).The high-performance liquid chromatography(HPLC)method was used to determine encapsulation efficiency and drug loading rate.Malvern particle size analyzer was used to measure particle size,Zeta potential,and polydispersity index(PDI).The morphology was observed through transmission electron microscopy.The dialysis method was used to determine the release rate.Results Sorafenib-disulfiram(1∶2,m/m)was the optimal drug synergistic ratio.The optimal process of CCD-RSM was as follows:the total drug dosage was 20.67 mg,the total material dosage was 140.54 mg,and the hydration volume was 8.22 mL.According to this process,the encapsulation efficiency of sorafenib was(94.2±0.03)%,and the drug-loading rate of sorafenib was(5.38±0.32)% .The encapsulation efficiency of disulfiram was(92.07±0.01)%,and the drug-loading rate of disulfiram was(7.89±0.32)% .The prepared nano micelles were spherical,uniformly dispersed,with a particle size of(61.36±0.74)nm,a Zeta potential of(-9.38±1.5)mV,and a PDI of 0.292±0.070.Under the environment with pH of 7.4,the release rates of sorafenib and disulfiram at 72 h were 58.70% and 14.90%,respectively.Under the environment with the pH of 7.4,the release rates of sorafenib and disulfiram at 72 h were 58.70% and 14.90%,respectively.Under the environment with the pH of 5.0,the release rates of sorafenib and disulfiram at 72 h were 97.20% and 28.60%,respectively.Conclusion Sorafenib/disulfiram-galactose-P123 micelles prepared by the thin film hydration method have excellent process,good stability,good encapsulation efficiency,pH sensitivity,and sustained release effect,which can effectively aggregate at the tumor site.
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