Preparation And Performance Study Of A Novel Tumor Targeted Drug Delivery System Based On Hyaluronic Acid-Folic Acid Modified Graphene Oxide

In this paper,graphene oxide was prepared by modified Hummers method and ultrasonic peeling dispersion method.The structure of graphene oxide was characterized by fourier transform infrared absorption spectroscopy,transmission electron microscopy and thermogravimetric analysis.The results show that there are abundant carbonyl,carboxyl and hydroxyl groups on the upper and lower surfaces and lamellar edges of the nano-sized graphene oxide.HA-GO nano-carrier materials targeting CD44 receptor were prepared,with hyaluronic acid and graphene oxide as raw materials,EDC and NHS as catalysts,adipate diacylhydrazide?ADH?as amino arm.FT-IR results show that the carboxyl groups of hyaluronic acid and graphene oxide and the amino groups of ADH were linked by amide bonds,which indicated that hyaluronic acid was grafted with graphene oxide successfully.HA-FA-GO drug carriers targeting CD44 receptor and folic acid receptor were prepared,with folic acid and HA-GO as raw materials,EDC and NHS as catalysts,ADH as amino arm.FT-IR results show that carboxyl groups of folic acid and graphene oxide and amino groups of ADH were linked by amide bonds.TEM results show that the thermal stability of the carrier composites was higher than that of graphene oxide.Which indicated that HA-FA-GO drug carrier had ligand components of CD44 receptor and folic acid receptor.This laid a good foundation for the development of drug carrier with dual targeting function for cancer.Doxorubicin hydrochloride?DOX?was loaded on HA-FA-GO drug carrier through non-covalent interaction.The effects of reaction temperature,stirring speed,pH value of reaction solution and mass ratio of drug to carrier on drug loading efficiency of DOX were investigated,L₉?3⁴?orthogonal experiments showed that the optimum preparation conditions of DOX/HA-FA-GO nano-drug delivery system were as follows:reaction temperature 25 C,stirring speed 150 rpm,acidic condition of pH5.8,2:5 mass ratio of drug to carrier.The in vitro drug release of DOX/HA-FA-GO nano-drug delivery system were observed by the dialysis.Drug release results showed that the release rate of the delivery system was different in PBS buffer at pH 5.8 and pH 7.4.The drug release rate in PBS buffer at pH 5.8 was higher than that in PBS buffer at pH 7.4 and the cumulative drug release after 72 hours was 70.98%.The results of mathematical model fitting showed that the best fitting effect was obtained between the release curve of DOX/HA-FA-GO nano-drug delivery system and the first-order equation dynamic model,which indicated that the new nano-drug delivery system had the potential for application of sustained-release preparations.