Construction Of XG-g-PAA/GO-DCFP Composite Hydrogel And Its Oral Administration

Graphene oxide（GO）is an important derivative of graphene with excellent physical and chemical properties,and is widely used in medicine field.GO can load compounds without destroying the original structure of the compound through hydrophobic interaction,π-πinteraction,hydrogen bonding and so on.With short half-life,fast absorption and irritation to the gastrointestinal tract,diclofenac potassium（DCFP）is not conducive to oral administration.In this study,DCFP was selected as a model drug to systematically study the mechanism of adsorption of DCFP by GO.The xanthan gum-graft-poly（acrylic acid）/graphene oxide（XG-g-PAA/GO）composite hydrogel was synthesized by in situ polymerization as a slow-release drug carrier.On this basis,the XG-g-PAA/GO-DCFP composite hydrogel was prepared,and the in vitro release and pharmacokinetic were studied.The main contents of this study are as follows:（1）Graphite oxide was successfully synthesized using the improved Hummers method,and the GO solution was obtained by dissolving graphite oxide and ultrasonic stripping it.Then,prepared GO was characterized.The results showed that the prepared GO had a two-dimensional sheet structure,and its surface and edges had successfully introduced oxygen-containing functional groups.The GO solution was uniformly dispersed and had good stability without aggregation or precipitation.（2）The loading efficiency and encapsulation efficiency were used as evaluation indicators to investigate the adsorption of DCFP by GO under different conditions.Different reaction models were used to fit the adsorption kinetics and adsorption isotherm model,respectively,to further explore the mechanism of adsorption of DCFP by GO.The results showed that the pseudo-second-order kinetic model and Freundlich model could better describe the adsorption of DCFP by GO.The dominant roles in the adsorption process wereπ-πinteraction and hydrophobic interaction,and there were hydrogen bonding and electrostatic interaction at the same time.（3）With xanthan gum（XG）and GO as raw materials,acrylic acid（AA）as the grafting monomer,N,N’-methylenebisacrylamide（MBA）and ammonium persulfate（APS）as the crosslinking agent and initiator of the reaction,respectively,the XG-g-PAA/GO composite hydrogel was synthesized.Meanwhile,the formulation optimization and characterization of the composite hydrogel were performed.Then,the XG-g-PAA/GO-DCFP composite hydrogel was prepared with DCFP as the model drug and the in vitro release experiment was performed.The results showed that the synthesized XG-g-PAA/GO composite hydrogel had a certain mechanical strength and uniform color,indicating that GO was evenly distributed in it.The results of swelling ratio test showed that the swelling ratio of XG-g-PAA/GO composite hydrogel increased significantly with the increase of pH value,showing pH sensitivity.We selected the optimal prescription for the XG-g-PAA/GO-DCFP composite hydrogel with the standard of loading efficiency.Under the optimal conditions,the maximum loading efficiency of XG-g-PAA/GO-DCFP composite hydrogel was 10.57%.The results of the in vitro release experiment showed that the cumulative release of DCFP（68.41%）after 96h under artificial intestinal fluid conditions was significantly higher than the cumulative release of DCFP（34.57%）after 96h under artificial gastric fluid conditions.These results showed that the XG-g-PAA/GO-DCFP composite hydrogel exhibit pH sensitivity under physiological conditions.（4）The DCFP and the XG-g-PAA/GO-DCFP composite hydrogel were administered by oral route respectively,and the results of in vivo pharmacokinetic research were obtained through analysis of relevant parameters.The results showed that the t_1/2 of the DCFP group was 2.03±0.35 h,while the XG-g-PAA/GO-DCFP composite hydrogel group was 10.71±2.04 h,indicating that the XG-g-PAA/GO-DCFP composite hydrogel prepared in this study could effectively prolong the drug action time.Moreover,the AUC_（0-t）of the DCFP group was53.99±3.18 mg/L*h,and the XG-g-PAA/GO-DCFP composite hydrogel group was116.79±14.72 mg/L*h,indicating that the DCFP prepared as a composite hydrogel could greatly improve bioavailability.The XG-g-PAA/GO-DCFP composite hydrogel can be further studied as a slow-release drug carrier in the future.