Strategy to design a smart photocleavable and pH sensitive chitosan based hydrogel through a novel crosslinker: a potential vehicle for controlled drug delivery

We report herein the synthesis of a novel photocleavable crosslinker, 4-formylphenyl 4-((4-formylphenoxy)methyl)-3-nitrobenzoate (CHO–ONB–CHO) and its joining with amine-based polysaccharides, viz. chitosan, resulting in the formation of a dual stimuli-responsive (ONB–chitosan) hydrogel having UV- and pH-responsive sites. The detailed mechanism for the formation of CHO–ONB–CHO and ONB–chitosan hydrogel is proposed. The (CHO–ONB–CHO) crosslinker was characterized using (1)H-NMR, LCMS and UV-visible spectroscopy. The dual responsive hydrogel is characterized by FTIR, SEM, XRD, DSC and TGA. The crosslinked hydrogel displayed mechanical robustness with a storage modulus of about 1741 pa. The pH-responsiveness of the hydrogel was studied via equilibrium swelling studies in various pH media at 37 °C. The photocleavable behavior of the crosslinker was observed in the UV-absorption range of 310–340 nm and the hydrogel exhibited maximum swelling at pH 5.7. The higher swelling of the hydrogel in acidic conditions and its photo-responsiveness can be exploited for the controlled, temporal and spatial release of therapeutic drugs at any inflammatory areas with acidic environments. It was observed that the hydrogel exhibited higher drug release at pH 5.7 than at pH 7.4.