Preparation and rectal administration of hydroxybutyl chitosan/graphene oxide composite thermosensitive hydrogel

Abstract

Recently, temperature-sensitive hydrogels have gained great interest as rectal gels. In this study, we selected temperature-sensitive hydroxybutyl chitosan gel (HBC) cross-linked with graphene oxide (GO) to improve biocompatibility. First, modified Hummer and ultrasonic stripping methods were used to synthesize stable GO dispersions. Pingyangmycin (PYM) as the model drug, the optimal drug loading process of GO@PYM was determined by the BBD model using encapsulation rate as the index of investigation. Then, HBC hydrogel was prepared by homogeneous etherification reaction. The 5%(wt) HBC hydrogel's gel time (Tgel) was 36.5 °C and gelation time was 30s. Finally, GO was cross-linked with HBC by hydrogen bonding to form HBC/GO composite hydrogel. Tgel was reduced to 31.7 °C. GO substantially enhanced the mechanical strength of HBC and the stability of HBC/GO structure. HBC/GO@PYM drug loading rate was approximately 8 times higher than HBC@PYM. The results of pharmacokinetic experiments showed that compared with HBC@PYM group, t1/2, MRT0-∞ (mean retention time) and AUC0-∞ (area under the curve) of HBC/GO@PYM group was 1.44, 1.51 and 2.31 times, respectively. HBC/GO effectively prolonged action time of the drug in-vivo by rectal administration, showed good sustained release effect, and significantly improved the bioavailability of PYM. HBC/GO@PYM can be further investigated by rectal administration.