功能化氧化石墨烯负载氟尿嘧啶制备及体外释放研究

Preparation and in Vitro Release of Functionalized Graphene Oxide Loading Fluorouracil

关键词:  功能化石墨烯  氟尿嘧啶  纳米粒  体外释放

Key words:  functionalized graphene  fluorouracil  nanoparticles  in vitro release

摘要:

目的 通过β环糊精(β-CD)功能化氧化石墨烯(graphene oxide，GO)负载氟尿嘧啶(5-Fu)，以增加5-Fu释放时间。方法 采用改进Hummers方法制备GO，使GO与β-CD酯化得到功能化GO-β-CD负载5-Fu。采用高效液相色谱法(HPLC)测定GO-β-CD-5-Fu的体外释放度。利用紫外、傅立叶变换红外、透射电镜、扫描电镜和拉曼光谱分别对GO，GO-β-CD，GO-β-CD-5-Fu表征测定。结果 GO功能化、负载均成功，负载率为105%。HPLC测定结果表明GO-β-CD-5-Fu突释效应减弱，呈梯度释放。T_1/2为(4.5±0.08)d。结论 GO-β-CD负载5-Fu成功，体外释放时间增加，T1/2提高了324倍。

Abstract:

OBJECTIVE To prolong the release time of 5-Fluorouracil(5-Fu) in vitro, β-cyclodextrin(β-CD) was used to functionalize graphene oxide(GO) and then loaded with 5-Fu. METHODS By using a modified hummers method to prepare GO, and the resulting GO could subsequently be esterified with β-CD to afford the β-CD functionalized GO(GO-β-CD). In addition, In vitro release of functionalized graphene oxide loading fluorouracil(GO-β-CD-5-Fu) could be determined by high performance liquid chromatography(HPLC). The structures and morphologies of GO, GO-β-CD and GO-β-CD-5-Fu were characterized by ultraviolet-visible(UV-vis) absorption spectroscopy, Fourier transform infrared(FTIR) spectroscopy, Transmission Electron Microscopy(TEM), Scanning Electron Microscopy(SEM) and Raman spectroscopy(Raman). RESULTS GO-β-CD were prepared and characterized successfully. GO-β-CD had a high drug loading capacity for 5-Fu, with a loading rate of 105%. The results of HPLC analysis showed the burst release effect of GO-β-CD-5-Fu was weakened in a gradient-release pattern,and the elimination half-life (T_1/2) was (4.5±0.08)d. CONCLUSION GO-β-CD was successfully loaded with 5-Fu and resulted in increase of the release time. Furthermore, GO-β-CD-5-Fu had a 324-fold longer T1/2 than 5-Fu.