Synthesis and characterization of a novel dual sensitive iron nanoparticles incorporated Schiff base composite hydrogel for diabetic wound healing therapy

Chronic wounds in diabetic patients deteriorate into multiple infections. A multifunctional transdermal material with high self-healing ability, remodeling capability, antibacterial and radicle scavenging activity, and an excellent multi-sensitive carrier was needed to promote wound healing. For that, Oxidized Cellulose (OC) and gelatin (GLN) are selected to construct a dual drug-loaded Schiff base hydrogel with iron nanoparticle (IONPS) incorporation for the controlled and sustained release of Insulin (INS) and Metfomin (MET), which synergistically promote wound repair. The INS/MET-IONPS-OC/GLN hydrogel drug payload was characterized using FT-IR, XRD, DLS, ZETA, TG, FE-SEM, TEM, and VSM analysis. The high drug loading and encapsulation efficiency were 93.20 % and 98.8 % for INS and 90.2 % and 95.1 % for MET, respectively. The temperature-sensitive drug release (92.0 % of INS and 90.0 % of MET) percentage is much better than the pH-sensitive drug release (83.5 % of INS and 80.2 % of MET). Above 90.0 % viability in MTT and apoptosis assay reveals the nontoxic nature of the INS/MET-IONPS-OC/GLN towards L929 normal cell lines. The zone of inhibition value of 12 and 15 mm in gram-negative bacteria reveals the anti-bacterial effect. The antioxidant activity of the carrier shields the cells against reactive oxygen species promotes healing rate ensures by DPPH assay.The cell proliferation and angiogenesis were confirmed by scratch assay on L929 cell lines in diabetic and non-diabetic conditions, showing the healing ability of the INS/MET-IONPS-OC/GLN hydrogel.