<i>Lepidium sativum</i> and metformin hydrochloride hydrogels for effective management of wounds in an induced diabetic rat model

Diabetic wounds need effective and prompt treatment otherwise, it will be complicated with sever bacterial infections. In this study, hydrogels containing <i>Lepidium sativum</i> seeds aqueous extract (LS_ae), metformin (MET) and combination (LS_ae and MET) were prepared and characterized for their pH, contents, spreadability, viscosity, rheology, morphology, physical stability and <i>in vitro</i> release. Percentage of wound contraction in streptozotocin induced diabetic rats was studied. In addition, certain biochemical parameters, like tumor necrosis factor-alpha, TNF-α, interleukin, IL-6, malondialdehyde, MDA and matrix metalloproteinase-9, MMP-9 as inflammatory and oxidative stress biomarkers were quantified. Histopathological changes were studied and immunohistochemical staining was used to detect vascular endothelial growth factor, VEGF and platelet endothelial cell adhesion molecule-1, PECAM-1/CD31. Pharmaceutical characterization revealed the suitability of hydrogels for topical administration. Combination hydrogel group 2 showed a significant reduction in TNF-α, IL-6, MMP-9 and MDA (296.36 ± 16.31, 8.33 ± 1.06 pg/ml, 0.61 ± 0.35 ng/ml and 13.30 ± 1.4 nmol/ml) compared to other tested groups. Histopathological examination showed complete re-epithelization with granulation tissue formation and thicker well-organized collagen fibers for groups 1 and 2 after 7 days. However, LS_ae hydrogel group 1 had a faster effect, a significant expression of VEGF (64.00 ± 17.08 positively stained cells) and (95.73 ± 2.4% wound contraction). It could be concluded that LS_ae hydrogel is a promising formulation for effective rapid management of diabetic wounds.