Synthesis and Anti-Abuse Performance Evaluation of PLGA-Tf Nano Drug Delivery System
Objective To investigate the preparation conditions of transferrin(Tf)-modified poly(lactic-co-glycolic acid)copolymer(PLGA)as a drug delivery system loaded with fentanyl analogues erastin,and to evaluate the stability,biocompatibility,and abuse-deterrent properties of the nanosystem in vitro.Methods The PLGA-Tf@Era was synthesized by the stepwise synthesis method.The effect of the mass ratio of PLGA-Tf to erastin on particle size and polydispersity index(PDI)was investigated.The morphology of PLGA-Tf@Era was detected by transmission electron microscopy.The particle size was detected by the Malvern laser particle size analyzer,and the structure was characterized by the sodium dodecyl sulfate-polyacrylamide gel electrophoresis silver staining test.The stability of PLGA-Tf@Era in different media[water,phosphate-buffered saline(PBS),fetal bovine serum(FBS),RPMI-1640 medium]within 7 d was detected in vitro,the extraction rate in ethanol and acidic aqueous solution(pH 5.1)and the incidence of hemolysis of 25,50,100 200,400 μg/mL PLGA-Tf@Era were detected.Results The optimal preparation conditions for PLGA-Tf@Era were as follows:the mass ratio of PLGA-Tf to erastin was 10∶1,the average particle size was 122 nm,the encapsulation efficiency was 82.20％,and the drug loading was 14.82％.The structural characterization test results showed that Tf and erastin were successfully loaded.Transmission electron microscopy examination results showed that PLGA-Tf@Era had a regular morphology,appearing spherical or quasi-spherical,with good dispersibility and no agglomeration phenomenon.The in vitro test results showed that the particle size and PDI of PLGA-Tf@Era in different media(water,PBS,FBS,RPMI-1640 medium)did not show significant changes within 7 d,and the morphology remained unchanged.When the drug concentration was below 100 μg/mL,the incidence of hemolysis was low,and the biological safety was good.The extraction rate of PLGA-Tf@Era was still lower than 21％after 12 h of extraction in the acidic aqueous solution(pH 5.1)and ethanol.Conclusion The synthesized PLGA-Tf@Era has suitable particle size,high drug loading capacity,and stable performance,which can be used to prevent the abuse of fentanyl-like drugs.
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维普
