Hyperglycemia induces the prostaglandin transporter (PGT) gene overexpression, leading to poor vascularization and wound healing. Dicer substrate small interfering RNA (DsiRNA) and gold nanoparticles (AuNPs) co-loaded into PF127 gel was developed to overcome the disturbance and infections. The AuNPs were biosynthesized using cold and hot water extracts of Lignosus rhinocerotis (abbreviated CLRE and HLRE, respectively). The wound healing efficacy of a PF127 gel containing DsiRNA-AuNPs-CLRE and -HLRE (assigned as F2 and F3, respectively) was evaluated in a diabetes-induced Wistar rat model. The F2 (DC) and F3 (DH) treated groups revealed a faster wound closure (92.67 ± 3.4% and 85.1 ± 7.3%, respectively) than the positive control (commercial gel, DTI)(74.9 ± 13.3%). DH and DC groups presented an increased blood vessel density, along with decreased number of inflammatory cells. In comparison to positive control, higher prostaglandin E2 (PGE2) (495 ± 79 and 50 ± 121 pg/mL, for DC and DH group, respectively), vascular endothelial growth factor (VEGF) (49 ± 15 and 38 ± 3 pg/mL, for DC and DH group, respectively) and VEGF-A levels were detected in both groups (DC and DH), indicating the effectiveness of DsiRNA in enhancing PGE2 production and vascularization. On evaluating microbiomes adhered to the wound areas, Gram-positive bacteria Staphylococcus and Corynebacterium, as well as Gram-negative Pseudomonas, Rodentibacter, and Acinetobacter, were found to be sensitive to the gel. Collectively, the gel was confirmed as a promising dressing for diabetic wound therapy, warranting further studies for clinical use.
Keywords: Gene silencing; Metal nanoparticles; Nanocomposites; RNA interference; Topical delivery.
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