Preparation And Antitumor Activity Of Bionic Gambogic Acid Nanoparticles Coated With Erythrocyte Membrane

Objective:To solve the problems of short half-life and poor water-solubility of gambogic acid（GA）,the bionic red blood cell（RBC）membrane coated GA nano drug delivery system（RBC@GPP-NPs）was prepared to enhance the water-solubility of GA,prolong the cycle time of GA,and improve the safety of GA.Methods:GA nanoparticles（GPP-NPs）were prepared by thin film dispersion method,and the particle size and encapsulation efficiency（EE）were used as evaluation indexes.According to the results of single factor test,the influencing factors in the preparation process of GPP-NPs were determined.The Box-Behnken effect surface method was used to screen the preparation conditions of GPP-NPs,so as to prepare GPP-NPs under the best process conditions.Then,the single factor experiment was carried out to determine the preparation process of RBC@GPP-NPs,and the particle size,Zeta potential,morphology,EE and stability of RBC@GPP-NPs were evaluated.The in vitro cumulative release of RBC@GPP-NPs was investigated by dialysis method,and the long-term circulation effect of GA was evaluated by the results of in vitro release test.The activity of the preparation was determined by inhibiting the growth of Hep G2.The safety of the preparation was evaluated by hemolysis test and the activity of L02 cells.Results:The optimal technological conditions for preparing GPP-NPs was as follows:drug loading ratio was 1:10,dosage ratio of normal saline to PEG₃₄₀₀-PLA₂₀₀₀was 0.17:1（m L:mg）,ultrasonic crushing power and time were 10%and 10 min,respectively,and centrifugation speed was 7000 rpm/min,the dilution factor of RBC membrane vesicles（RVs）was 4 times,and the ultrasonic crushing time was 3 min.The average particle size of RBC@GPP-NPs is（98.48±0.72）nm,and the particle size distribution is concentrated and spherical.Zeta potential was（-6.96±0.60）m V.EE was（79.11±1.42）%;RBC@GPP-NPs placed at 4℃for 16 days has good stability;in the release time of RBC@GPP-NPs in vitro,the in vitro release time of RBC@GPP-NPs was significantly longer compared with GPP-NPs.In the in vitro activity and safety studies,it was found that,compared with GA and GPP-NPs,although RBC@GPP-NPs had slightly lower antitumor activity,it had a lower erythrocyte hemolysis rate and higher safety.Conclusions:GPP-NPs nanoparticles prepared by thin film dispersion method can successfully bind RBC membrane to the surface of GPP-NPs by co-incubation with RVs and extruding with an extruder,so that RBC@GPP-NPs can obtain a long cycle effect,retain the anti-liver cancer activity of GA,and improve the safety of GA.