Study On The Preparation And The Anti-tumor Activity Of Folate-targeted TanshinoneⅡ_A-loaded BSA Nanoparticles

Objective The paper was to prepare nanoparticles(NPs) by using bovine serum albumin(BSA) as the carrier material and tanshinoneⅡA(TanⅡA) which was a liposoluble component extracted from Salvia as the main drug. The Tan ⅡA loaded BSA NPs were modified with folic acid(FA) by EDC and NHS activation method. Through examining the effects of FA-TanⅡA-BSA NPs on tumor targeting and tumor cell viability, it proved that the folate acid conjugated NPs have more positive significance of tumor treatment.Methods Tanshinone Ⅱ A-loaded BSA nanoparticles(TanⅡA-BSA NPs) were prepared by using desolvation method. Drug encapsulation efficiency and in vitro release of the obtained NPs were thoroughly investigated. Box-Behnken experimental design and response surface methodology were applied to optimize the preparing conditions. Folic acid-modified BSA NPs were prepared by coupling reactions using EDC and NHS, and the connection of folic acid and BSA-NPs was confirmed by the changing of the particle size. Cell viability test was conducted for biocompatibility of the prepared NPs, and the cytotoxicity and cellular uptake of the NPs were also investigated by using hepatoma cell SMMC-7721 cell.Results The optimal values of the ratio between drug and BSA, the ratio between H2 O and ethanol, and dripping speed of ethanol were determined to be 0.09,0.53, 1.27 m L/min respectively. The predicted values and experimental values were relatively accordant, thus the model showed good prediction. Drug encapsulation efficiency was 84.35% and the release pattern showed a long and biphasic drug release. MTT results showed that, compared with the free TanshinoneⅡA, the viability of cells treated with FA-TanⅡA-loaded BSA NPs was significant decreased. Uptake results proved that NPs were uptaken through endocytosis, and after the decoration, intake of FA-TanⅡA-loaded BSA NPs were more excellent.Conclusions BSA nanoparticles were successfully prepared by using desolvation method. The NPs showed good monodispersity, homogenous particle size, first- order release characteristic, better cellular uptake and cell inhibition rate of nanoparticles coupled with folate also the nano carrier BSA was nontoxic.