Self-healing quercetin loaded hyaluronic dialdehyde conjugated aminoethyl-β-cyclodextrin and chitosan hydrogel via Schiff base reaction for enhanced anti-inflammatory activity

Abstract

In this work, hydrogels composed of hyaluronic dialdehyde (HAD) and amino-beta-cyclodextrin (ACD) incorporated with quaternary ammonium chitosan (HACC) were synthesized in situ via Schiff base reaction. The composition, morphology and mechanical properties were characterized using FTIR, 1H-NMR, SEM and rheological testing. Hydrogels were prepared using different molecular weights of HAD. The results showed that a higher molecular weight of HAD has increased the swelling ratio up to 1715-1835% and enhanced the mechanical properties of hydrogels. Increasing the HAD content further improved stability and mechanical properties due to a higher degree of crosslinking. Quercetin (Que), was used as a hydrophobic drug to form an inclusion complex with ACD and was loaded in HAD-ACD-HACC hydrogels. Drug release, cytotoxicity and anti-inflammatory activity were investigated in vitro. The results indicated that quercetin release was higher in acidic media than in neutral solutions. Cellular assessment of quercetin loaded 100k-2 and 1M-2 hydrogels by scratch test encouraged the migration of human keratinocyte (HaCaT) cells. The anti-inflammatory activity of quercetin loaded 100k-2 hydrogel was improved compared to free quercetin against HaCaT cells. Thus, this quercetin-loaded hydrogel system offers a promising approach for controlled drug release, enhanced anti-inflammatory and wound healing activities in various biomedical applications.