The Study On Taurine-Grafted Nano Graphene Oxide As Drug Delivery System

In recent years,due to the excellent properties of graphene oxide(GO)in optics,electromagnetism,thermodynamics etc,more and more researchers focus on the biological and pharmaceutical fields.So we made use of Taurine,a non-essential amino acid with a good biocompatibility,to modified GO by the covalent bond to obtain the functional GO.And we chose 5-fluorouracil(5-FU)as model drug to improve its porr bioavailability through the constructed system.In this study,we studied the synthesis,preparation characterization,pharmacokinetics and cell experiments of a nano-delivery system on 5-FU by taurine-grafted nano graphene oxide.At the same time,we made use of computer simulation test to lay a corresponding theoretical basis for our study.The main contents of this study are as follows:(1)Nano-sized GO was synthesized by the modified Hummers method and ultrasonic stripping method.Then,prepared GO was characterized by other methods.After that,taurine was modified to the surface of GO by the chemical bonds get taurine-modified graphene oxide carrier(Tau-GO).The Tau-GO was characterized.The result of characterization showed that Tau-GO had a lamellar structure with no obvious aggregation and was fairly stable.In addition,we could conclude that the degree of the modification of Tau on GO was about 13%.(2)We made use of the orthogonal design method to select the optimal prescription for the 5-FU-Tau-GO drug delivery system with the standard of encapsulation efficiency.Then,under the optimal conditions,the maximum encapsulation efficiency of Tau-GO carrier to 5-FU could be 83.2%.Then we simulated the in vitro release environment pH 1.2,pH 6.5 and pH 7.4 to explore the feature of in vitro release of 5-FU-Tau-GO drug delivery system.As a result,the constructed 5-FU-Tau-GO drug-loading system could realize the pH-responsive release in the acidic microenvironment of the tumor and and minimized the toxic side effects on normal tissues.(3)We studied the in vivo release characteristics of the 5-FU and 5-FU-Tau-GO through the oral and intravenous routes by the in vivo pharmacokinetic test.The result showed that whether it was administered by oral or intravenous route,5-FU-Tau-GO prolonged the effective time of 5-FU,and improve its bioavailability.(4)The inhibition of 5-FU,Tau-GO and 5-FU-Tau-GO on human hepatoma cells(HepG2)was studied by MTT assay.To better observe the effects of different administration groups on the morphology of HepG2 cells,AO/EB staining was tested.The results showed that Tau-GO had almost no lethality against HepG2 cells,and the inhibition of 5-FU-Tau-GO on HepG2 cells was enhanced compared with 5-FU in the same concentration,and it could significant change of the morphology of HepG2.(5)The molecular docking and molecular dynamics simulation was studied between 5-FU and Tau-GO through computer simulation test.As a result,the system of Tau-GO and 5-FU was more stable than the unmodified GO and 5-FU,which meant the 5-FU-Tau-GO is more effective for the delivering and releasing of 5-FU.