Soft hydrogel based on modified chitosan containing P. granatum peel extract and its nano-forms: Multiparticulate study on chronic wounds treatment.

Punica granatum peel (PGP) is widely used in traditional medicinal purposes for chronic wounds owing to containing natural phenolics active components. In current study, active wound dressing hydrogel for chronic wound healing was prepared based on P. granatum peel crude extract (PGPC), ethyl acetate fraction (PGPEA) and their silver nanoforms (Ag-NPs). Methacrylated chitosan was synthesized as precursor to hydrogel and crosslinked by divinyl sulfone (DVS) in mild condition. Hydrogel was fully characterized by spectral morphological, mechanical and physical analyses. The integration of PGPEA silver nanoforms was formed with particle size of 15-56 nm to show minimum inhibitory concentration (MIC) equal 63 for Staphylococcus aureus and 125 for Pseudomonas aeruginosa. The hydrogel-based wound dressing with/without the active ingredients showed acceptable cytotoxicity against fibroblast human cells for PGPC and PGPEA fraction over the silver nanoforms. Rat as animal model was considered to show the impact of the active wound dressing on diabetic wounds which was proved by histopathological examination. In addition, the significant intensity of immunopositivity signals of the transforming growth factor beta (TGF-β1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the epidermal cells have revealed the efficiency of Ag NPs-PGPEA-chitosan hydrogel for chronic wound curing.