Injectable self-healing oxidized pectin and carbohydrazide-modified gelatin hydrogels for curcumin-loaded zein...

The design of drug delivery systems (DDS) for efficient and sustained in situ antioxidant treatment is demanded in regenerative medicine applications. DDS, based on nanoparticle-loaded hydrogels, are promising advanced drug delivery platforms to achieve prolonged release and targeted bioactivity. Herein we developed innovative and sustainable injectable hydrogels based on oxidized pectin (PDA) and carbohydrazide-modified gelatin (G-CDH) for the release of curcumin-loaded zein nanoparticles (CurZNPs) for mitigating cell oxidative stress. CurZNPs, produced by nanoprecipitation, exhibited high encapsulation efficiency, sustained curcumin release, and strong antioxidant and anti-inflammatory activities. PDA/G-CDH hydrogels with three different PDA : G-CDH ratios were prepared by double physical and chemical crosslinking, through calcium ions internally released from CaCO₃ and Schiff base formation between PDA and G-CDH functional groups, respectively. PDA/G-CDH hydrogels showed rheological tunability, depending on the degree of pectin oxidation (2.5 mol%: PDA_2.5 and 5 mol%: PDA_5). Hydrogels with a balanced aldehyde-to-amine ratio, specifically the PDA_2.5/G-CDH (70 : 30) and PDA_5/G-CDH (50 : 50) formulations, were selected based on their superior stability in physiological conditions, consistent with effective crosslinking. Such compositions also exhibited injectability through shear thinning behaviour, and self-healing by restored mechanical integrity after stress, and supported human fibroblast viability and attachment. CurZNPs-loaded PDA/G-CDH hydrogels showed prolonged curcumin release, antioxidant activity by restoring fibroblast viability after induced oxidative damage, and anti-inflammatory properties with RAW 264.7 macrophages. In conclusion, injectable PDA/G-CDH hydrogels were efficient and biocompatible DDS for antioxidant treatment through controlled CurZNPs release.