叶酸修饰的藤黄酸纳米晶-磷脂复合递药系统的制备及评价OA

Objective In order to improve the targeting release of gambogic acid,a folic acid-modified gambogic acid nanocrystals-phospholipid composite drug delivery system(GA-NCs@PL-FA)was designed and prepared,and its prescription process was optimized.The physicochemical properties,in vitro anti-hepatocarcinoma activity and in vivo tissue distribution characteristics of GA-NCs@PL-FA were investigated.Methods Gambogic acid nanocrystals(GA-NCs)were prepared by CO2-assisted precipitation method,and then GA-NCs@PL-FA was constructed by thin film hydration method.The prescription process was optimized by single factor investigation and central composite design-response surface methodology(CCD-RSM).The microscopic morphology was observed by transmission electron microscopy(TEM),and the particle size,ζ potential,encapsulation efficiency,drug loading and stability were determined.The in vitro release behavior in pH 7.4,6.5 phosphate buffer(PBS,containing 0.5％Tween 80)was investigated by dialysis bag method.The effects of different administration groups on the viability and migration ability of HepG2 cells were evaluated by cell counting kit-8(CCK-8)method and cell scratch test.The content of gambogic acid in each tissue of tumor-bearing nude mice was determined by ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),and its tissue distribution and tumor tissue enrichment ability were analyzed.Results The GA-NCs@PL-FA was spherical,the particle size was(183.07±0.55)nm,the ζ potential was(-17.70±0.17)mV,the encapsulation efficiency and drug loading were(84.64±0.57)％and(4.33±0.07)％,respectively.The properties were stable after 7 d at 4,25 ℃.In both release media,it showed obvious sustained release effect.In vitro experiments showed that compared with gambogic acid,GA-NCs and folic acid-free gambogic acid nanocrystals-phospholipid composite drug delivery system(GA-NCs@PL),GA-NCs@PL-FA had a stronger inhibitory effect on the proliferation and migration of HepG2 cells,and the half inhibitory concentration(IC50)was reduced to 0.50 μg/mL.The tissue distribution test confirmed that GA-NCs@PL-FA could prolong the retention time of gambogic acid in vivo and promote its enrichment in tumor tissues,with good targeting.Conclusion The formulation and preparation process of GA-NCs@PL-FA were optimized.The system had uniform particle size,good drug loading performance,good sustained release effect and in vitro anti-hepatoma activity,and showed strong tumor tissue enrichment ability.It can provide reference for the development and clinical application of gambogic acid targeted preparations.