Designing biocompatible functional network pH-sensing hydrogels for automated colonic therapeutic delivery

Abstract

Currently, significant advancements are underway in research and technology exploring bioactive polysaccharides and designing materials for applications in clinical and healthcare products for sustainable development. Herein, functionalization of bioactive carrageenan (CG) and tragacanth gum (TG) polysaccharides was carried out using a phosphate polymer for fabrication of hydrogels as drug delivery (DD) carriers via covalent linkage through a copolymerization reaction, supplemented by supramolecular interactions. The copolymers were characterized via FESEM, EDAX, FTIR, ¹³C-NMR and XRD. Furthermore, the biocompatibility, antioxidant, mucoadhesion, enzymatic degradation, protein adsorption, antimicrobial, colonic fluid sorption, and drug delivery properties of the hydrogels as well as their effect on rhabdomyosarcoma cell viability were analyzed. The hydrogels showed 156% ± 0.14% cell viability and promoted the proliferation of RD cells, demonstrating their compatibility with mammalian cells. Furthermore, the DPPH assay revealed 42.43% ± 1.01% free radical inhibition, highlighting their potent antioxidant character. The adhesion capacity of the materials was demonstrated by the fact that a force of 129 ± 2.12 mN was required for the separation of the hydrogels from the mucosal surface, indicating their compatible mucoadhesive nature. The hydrogels were also susceptible to enzymatic degradation, wherein their maximum degradation was observed in a cecal-mimicking colonic environment. The mechanism of drug diffusion from the encapsulated hydrogels was governed by non-Fickian diffusion, and thus, their release profile was best described by the Higuchi kinetic model. The cumulative drug release pattern was also studied, and results indicated the effectiveness of the intestine-targeted delivery system with minimal drug release in an upper GIT simulated medium. However, in a colonic environment, more drug release occurred under alkaline conditions, suggesting its potential for maintaining a prolonged therapeutic effect in the colon. Overall, a thorough assessment of the results of the various physico-chemical, biomedical and DD properties of the hydrogels suggested that these polysaccharide-derived hydrogels are suitable materials for fabricating colon-targeted DD systems.