Development of A Thermo-pH Responsive Hydrogel for Oral Delivery of Anti-Diabetic Nutraceuticals

Abstract

Nutraceuticals derived from medicinal plants, which have both nutritional and pharmaceutical values, are mostly volatile and prone to degradation caused by gastric juice. So, this study focuses on two key areas: the optimization of synthesis of chitosan-cyclodextrin-g-glutamic acid/glycerophosphate (CS-CD-g-Glu/GP) based hydrogel, as well as the encapsulation and delivery of nutraceuticals derived from Adhatoda Zeylanica using the hydrogel matrix. In this hydrogel synthesis, crucial factors that greatly impact the process include gelation time, solubility, pH, and mixing duration. The concentration of (CS-CD-g-Glu), the ratio of CS to CD-g-Glu, and the ratio of GP solution to CS-CD-g-Glu solution were considered as variables for optimizing the synthesis process of hydrogel. Gelation time was recorded for each hydrogel, and the composition of hydrogel having the fast gelation and pH (6.8-7) was taken as the optimized one. In optimized hydrogel, the composition of CS-CD-g-Glu was 3 (w/v)%, the ratio of CS to CD-g-Glu was 2:1, the ratio of CS-CD-g-Glu solution to 50 wt% GP solution was 2:1, and the gelation time was 15 minutes at 37℃. Later, extracted essential oil (EO) was encapsulated into the optimized hydrogel by adding EO in an intermediate step of hydrogel synthesis, and the sol-state was formulated following the same procedure of hydrogel formation. One of the synthesized components of hydrogel, CD-g-Glu, was analyzed using NMR spectroscopy, and the spectral analysis confirmed the successful synthesis of CD-g-Glu. The freeze-dried hydrogel matrix was studied for functional group analysis using FTIR and morphological analysis using Scanning Electron Microscope (SEM). PH sensitivity of the synthesized hydrogel was demonstrated using swelling test which showed higher swollen ratio in the acidic pH compared to basic pH. Additionally, the study examined rheological parameters, focusing on the behavior of the hydrogel at varying temperatures, along with the results from amplitude sweep tests and flow curve analyses. The hydrogel showed sol to gel transition temperature of 37 ℃, and its viscoelastic nature was also proven from rheology. Finally, in vitro release studies of the EO-encapsulated hydrogel demonstrated a release of approximately 88 wt% vasicine in acidic pH and 62.43 wt% in basic pH over 24 hours. These results indicate that the synthesized hydrogel efficiently encapsulates the essential oil with antidiabetic properties and enables controlled release of the EO.