Synthesis of chitosan-graphene oxide thermosensitive in situ hydrogel for nasal delivery of rasagiline mesylate: In-vitro-ex vivo characterization

Abstract

Intranasal administration of a drug offers a way to bypass the blood-brain barrier, allowing for an increased drug concentration in the brain and improved bioavailability. In this context, the preference for polymeric thermoresponsive intranasal hydrogels has been widely documented. Here, there is a need to enhance the physical properties of the hydrogel and improve control over the release of the drug. In this work, we propose the incorporation of graphene oxide (GO) into a thermosensitive in situ hydrogel (RM@CS/B-GP-GO) based on chitosan (CS) and beta-glycerophosphate (B-GP) for intranasal delivery of rasagiline mesylate (RM). The prepared in situ hydrogel formulations were characterized using gelation temperature, gelation time, swelling, porosity, gel strength, mucoadhesive strength, pH, morphological features, spectral analysis, drug release, permeation study, and so on. In this work, the incorporation of GO showed a significant concentration-dependent effect on the properties of the thermosensitive CS hydrogel. In brief, the addition of GO in RM@CS/B-GP decreased the gelation time, porosity, and swelling of the hydrogel. Additionally, CS-hydrogel strength increased with higher concentrations of GO. The RM@CS/B-GP-GO hydrogel (1 mg/mL of GO) showed the customized release of RM almost 68.41 ± 2.01 % in 8 h than the RM@CS/B-GP hydrogel (log p < 0.05). Based on these findings, the physical and mechanical properties of the RM@CS/B-GP-GO thermosensitive hydrogel were improved by the addition of optimized concentration GO. Moreover, RM@CS/B-GP-GO hydrogel shows good biocompatibility with nasal mucosa. Overall, the design of RM@CS/B-GP-GO can open new options for the delivery of RM through the nasal route.