Dual pH-/thermo-responsive chitosan-based hydrogels prepared using click chemistry for colon-targeted drug delivery applications

A dual pH-/thermo-responsive hydrogel was designed based on a polyelectrolyte complex of polyacrylic acid (PAA) and norbornene-functionalized chitosan (CsNb), which was synergized with chemical crosslinking using bistetrazine-poly(N-isopropyl acrylamide) (bisTz-PNIPAM). The thermo-responsive polymeric crosslinker, bisTzPNIPAM, was synthesized via reversible addition-fragmentation transfer polymerization of NIPAM. FTIR, XRD, rheological and morphological analyses demonstrated the successful formation of the polyelectrolyte network. The highly porous structure generated through the in-situ click reaction between Tz and Nb resulted in a higher drug loading (29.35 %). The hydrogel (COOH/NH2 mole ratio of 3:1) exhibited limited drug release (8.5 %) of 5ASA at a pH of 2.2, but it provided an almost complete release (92 %) at pH 7.4 and 37.C within 48 h due to the pH responsiveness of PAA, hydrogel porosity, and shrinkage behavior of PNIPAM. The hydrogels were biodegradable and non-toxic against human fibroblast cells, suggesting their considerable potential for a colontargeted drug delivery system.

Automated summary

A dual pH-/thermo-responsive hydrogel was successfully designed using a polyelectrolyte complex and chemical crosslinking, demonstrating high drug loading capacity and controlled drug release properties at different pH levels, showing promising applications in colon-targeted drug delivery systems.