Chitosan hydrogel incorporating ferulic acid polymeric nanosponges for enhanced diabetic wound repair in streptozotocin-induced mice

초록

Diabetic wound repair presents complex pathophysiology due to hyperglycemia, oxidative stress, and prolonged inflammation. Despite anti-diabetic wound repairing potential, Ferulic acid (FA) limited by poor biopharmaceutical properties and low stability. Therefore, FA-loaded polymeric nanosponges (FA-NS) were prepared, statistically optimized using Box-Behnken design (BBD), and characterized using Dynamic light scattering (DLS), Transmission electron microscopy (TEM), Scanning electron microscopy (SEM), Energy dispersive X-ray spectroscopy (EDXS), Fourier transform infra-red (FTIR) spectroscopy, X-ray diffraction (XRD), and Differential scanning calorimetry (DSC). FA-NS were further incorporated into chitosan hydrogel to develop FA-NS-CG for topical application, which was evaluated by in vitro and ex vivo in comparison to FA-dispersion and FA-conventional gel. Moreover, in vivo investigations were performed in streptozotocin (STZ) induced diabetic mice wound model. The optimized FA-NS exhibited particle size of 234.3 +/- 0.14 nm, narrow size distribution (PDI = 0.141 +/- 0.01), zeta potential of -17.4 +/- 0.98 mV, and higher entrapment efficiency (<90%). TEM and SEM analysis exhibited spherical and 3-D shaped FA-NS. FTIR exhibited no chemical interactions whereas, XRD showed that the FA lost its high crystallinity when entrapped in the nanosponges. Furthermore, FA-NS-CG demonstrated optimum viscosity, pseudoplasticity, and good spreadability for diabetic wound application. Moreover, it showed a sustained in vitro release profile and 3.66-fold higher enhancement ratio when compared with FA dispersion, FA-NS, and FA-CG. In vivo wound study on STZ-induced diabetic mice demonstrated enhanced wound contraction, collagen deposition, and re-epithelization. Overall, findings establish FA-NS-CG as a promising topical nanoformulation for accelerating diabetic wound repair through sustained release, enhanced skin permeation, and improved tissue regeneration.

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