Efficiency and Safety of β-CD-(D3)7 as siRNA Carrier for Decreasing Matrix Metalloproteinase-9 Expression and Improving Wound Healing in Diabetic Rats

Overexpression of matrix metalloproteinase-9 (MMP-9) is critical for diabetic chronic wounds involved in the refractory wound healing process. We aimed to develop a strategy through RNAi to decrease MMP-9 expression and improve diabetic wound healing. We had explored beta-CD-(D-3)(7) as a gene carrier to take siRNA and effectively interfere with MMP-9 expression. It has been proven that beta-CD-(D-3)(7) could be used as an effective siRNA delivery system. In this study, we want to know about the efficiency and safety of beta-CD-(D-3)(7)/MMP-9 siRNA for improving wound healing in diabetic rats. beta-CD-(D-3)(7)/MMP-9 siRNA treated animals show lower levels of MMP-9 expression, which induce faster wound-close rates. Histological evaluation indicates that beta-CD-(D-3)(7)/MMP-9 siRNA significantly increases the content of collagen around the injured tissues. The number of neutrophilic ganulocytes was significantly decreased through treatment of beta-CD-(D-3)(7)/MMP-9 siRNA. In vivo fluorescence imaging assessment shows that beta-CD-(D-3)(7)/MMP-9 siRNA could not cause organ damage and organ accumulation. The results suggest that beta-CD-(D-3)(7)/MMP-9 siRNA might be developed as a novel topical agent for the diabetic wounds treatment.