In Silico Assessment of Doxycycline Monohydrate MMP-9 Inhibition and Preparation and Evaluation of Doxycycline chitosan nanoparticle for Diabetic wound

A significant worldwide health concern is chronic wounds related to diabetes mellitus (DM), frequently leading to excised due to impaired healing processes exacerbated by secondary infections (e.g., Staphylococcus aureus and Escherichia coli ), neuropathy, and endothelial dysfunction. Doxycycline, recognized for inhibiting matrix metalloproteins (MMP-9), is essential for improving angiogenesis, cell migration, keratinocyte, and extracellular matrix (ECM) formation for diabetic wound healing. This study explores the molecular interaction of doxycycline monohydrate with MMP-9 through in silico docking simulations using ArgusLab for protein preparation and BIOVIA Discovery Studio to analyze binding conformations and energy levels. Doxycycline-loaded nanoparticles (DOX-NPs) were synthesized using the ionic gelation process and characterized by the entrapment efficiency, Zeta potential, polydispersity index (PDI), size of the particle, FTIR spectra, and TEM. In vitro evaluations, encompassing antioxidant properties, drug release, antibacterial efficacy, cytotoxicity, and scratch assays on L929 fibroblast cells, revealed that DOX-NPs enhanced wound healing. The significant binding affinities between doxycycline and MMP-9 indicate the potential effectiveness of DOX-NPs application in diabetic wounds.