PIOGLITAZONE-LOADED NANOSTRUCTURED LIPID CARRIERS INCORPORATED INTO A COLLAGEN-CHITOSAN COMPOSITE SCAFFOLD FOR DIABETIC WOUND HEALING

Diabetic wounds represent a serious clinical complication and frequently progress to limb or tissue amputation in individuals with diabetes mellitus. One of the primary reasons for impaired wound repair in diabetic conditions is the prolonged inflammatory phase, which interferes with subsequent stages of healing and results in delayed or incomplete tissue regeneration. Pioglitazone hydrochloride (Pio), a well-established antidiabetic agent, has also been reported to exhibit significant anti-inflammatory activity. In the present work, a pioglitazone-loaded nanostructured lipid carrier (Pio-NLC) incorporated into a collagen–chitosan (COL-CS) scaffold was developed and evaluated for its therapeutic potential in diabetic wound healing. Physicochemical characterization demonstrated that chemically cross-linked composite scaffolds exhibited optimal porosity, reduced degradation rate, and prolonged drug release when compared to non-cross-linked formulations. In vitro biocompatibility studies confirmed that the Pio-NLC- COL-CS scaffold supported enhanced cellular proliferation relative to control and NLC-COL-CS scaffolds without drug loading. Furthermore, in vivo evaluation using a streptozotocin-induced diabetic wound model showed a significantly greater rate of wound closure (p < 0.001) in animals treated with the Pio-NLC- COL-CS scaffold compared to control and NLC-COL-CS-treated groups. Enzyme-linked immunosorbent assay findings revealed a marked reduction (p < 0.001) in matrix metalloproteinase-9 levels in the Pio-NLC-COL-CS group, indicating suppression of excessive inflammatory activity. Overall, the developed pioglitazone-loaded nanostructured lipid carrier scaffold demonstrates strong potential as an effective localized therapeutic approach for the management of diabetic wounds.