ABSTRACT
Objective: The formulation of co-loaded docetaxel(DTX) and gambogic acid(GA) albumin nanoparticles(DTX-GA-BSA NPs) was optimized by central composite design-response surface methodology to prepare DTX-GA-BSA NPs, and its quality was evaluated. The optimal synergistic ratio of DTX and GA was screened by coefficient of drug interaction(CDI). Method: NabTM method was used to prepare DTX-GA-BSA NPs with bovine serum albumin(BSA) as the carrier material. Design-Expert 8.0.6 software was used to design the experiment and process the data, overall desirability(OD) of particle size and polydispersity index(PDI), encapsulation rate were taken as indexes. The particle size and Zeta potential of the nanoparticles were measured. Individual and synergistic inhibitory effects of DTX and GA on the proliferation of MGC-803 and HGC-27 cells were determined by methyl thiazolyl tetrazolium(MTT) assay, respectively. Result: The optimum prescription of DTX-GA-BSA NPs was as follows:BSA concentration of 5 g·L-1, water-oil phase volume ratio of 1:17, drug-loading ratio(mass ration of drug to carrier) of 1:10.The average particle size of DTX-GA-BSA NPs was 135.8 nm and PDI was 0.09, Zeta potential was -21.4 mV. The deviation between the predicted value and the observed value of the model was small, the model had good predictability. For MGC-803 cell, when the concentrations of DTX and GA were 0.004, 0.12 μmol·L-1, respectively(mass ratio of DTX to GA was 1:23), the CDI value was the smallest and the synergistic proliferation inhibition was the most significant. For HGC-27 cell, when the concentrations of DTX and GA were 0.004, 1 μmol·L-1, respectively(mass ratio of DTX to GA was 1:195), the synergistic proliferation inhibition was the most significant. Conclusion: The optimized formulation of DTX-GA-BSA NPs is stable and reliable. The established mathematical model has good predictive ability and practicability. DTX combined with GA has synergistic effect on MGC-803 and HGC-27 cells without concentration dependence.