Pioglitazone-loaded three-dimensional composite polymeric scaffolds: A proof of concept study in wounded diabetic rats.

Diabetic patients suffer from impaired wound healing. In this study, the anti-diabetic drug, Pioglitazone hydrochloride (PG), was loaded in three-dimensional (3D) composite scaffolds (SC) designed to be applied topically for the management of diabetic wounds. Hydroxypropyl methyl cellulose (HPMC) of different molecular weight (E5, K4M or K15M) were used, in different ratios, with chitosan (CS) for the preparation of the 3D-SC. Investigations to examine the prepared SCs revealed that SC-F3 composed of CS /HPMC E5 (2:1) attained the highest porosity (99.12 ± 5.01), highest water absorption capacity % (300.09 ± 20.20), and attained the fastest drug release profile (p < 0.05), with release kinetics following the diffusion model. SEM microphotographs showed the highly porous structure of SC-F3. According to the modified Draize test, the selected 3D-SC (the medicated as well as the unmedicated) showed to be safe for skin application (PII = 0). During the in-vivo studies, both the selected PG-loaded SC and the unmedicated SC showed a significant improvement in the healing process compared to the untreated group, this was evidenced by the measurement of wound contraction % [627% and 467%, respectively, p < 0.05], as well as the level of some biomarkers (TNF-α, VEGF and MMP-9). PG-loaded SC had a significantly better effect than the unmedicated SC (p < 0.05). Histopathological studies confirmed the complete tissue regeneration and healing process after the use of the selected PG-loaded scaffolds. The current study presents a feasible approach to support diabetic wound healing using a simple and safe formulation.