ABSTRACT
OBJECTIVE:To prepare Bevacizumab(BEV)multivesicular liposomes(BEV-MVLs)with sustained-effect,and to study their in vitro release characteristics. METHODS:BEV-MVLs were prepared by double emulsion method. Box-Behnken design-response surface methodology was used to optimize the prescription with the concentration of glycerol trioleate(TO)in organic phase,ratio of 1,2-dioleoyl-sn-glycero-3-phosphocholine(DOPC)-cholesterol(CH)(mol/mol),the concentration of L-lysine in external water phase as factors,using encapsulation rate as index. The morphology of BEV-MVLs was observed by inverted fluorescence microscope and SEM;particle size was determined by laser particle size analyzer;the BEV content was determined by HPLC and calculate the encapsulation rate and in vitro accumulative release rate.RESULTS:The optimized prescription was as follows as TO of 2.72 mmol/L in organic phase,DOPC-CH ratio of 0.67(mol/mol)and L-lysine of 40 mmol/L in external water phase. The encapsulation rate of BEV-MVLs was(80.65±4.42)%(n=3),and relative error of it to predicted value was 2.54%. The liposomes were spherical in appearance shape and uniform in size,and they were typical non-concentric vesicle structure with average particle size of 16.80 μm. 30 d in vitro accumulative release rate was about 92%. CONCLUSIONS:Prepared BEV-MVLs show sustained-effect,and their encapsulation rate reaches the expected effect.