Harnessing chitosan for zinc and hydroxychloroquine delivery, interactions with fibronectin, and antibacterial activity

Chitosan, a natural polysaccharide derived from chitin, has gained attention for its dual role as an effective delivery method and as an antibacterial agent. Chitosan was selected as an efficient carrier for zinc (Zn) and hydroxychloroquine (HC) due to its ability to mitigate their adverse effects. The nanocarrier helps prevent harmful impacts on the host, with chitosan's biocompatible and biodegradable nature making it an ideal choice. Fibronectin, a glycoprotein extensively found in extracellular fluids and matrices of various tissues, serves as a common target for many microorganisms. Molecular docking studies revealed that the Zn, HC and Chitosan inhibit the fibronectin protein of Streptococcus and Staphylococcus species. We developed a novel formulation combining chitosan, zinc oxide, and hydroxychloroquine to enhance the delivery of Zn and HC. The formulation was characterized using TEM, elemental analysis, particle size analyzer and FTIR. Fluorescent microscopy using FluoZin-3 on bacterial cultures confirmed the presence of zinc on the surface of the organisms. Further, we investigated successfully its antibacterial effects against Streptococcus equi . ZnO nanoparticles (NPs) excel in bacterial inhibition but are limited by cytotoxicity. In contrast, the Ch-ZnHC Complex, slightly less potent, offers a safer profile for host cells. Despite containing trace zinc, it effectively inhibits bacterial growth, likely due to a synergistic interaction between chitosan, zinc, and HC. This balance of antimicrobial efficacy and low toxicity makes the Ch-ZnHC Complex ideal for applications demanding prolonged exposure or higher safety standards. This study is the first to explore the inhibitory activity of this complex against S. equi , emphasizing its potential as a safe and effective alternative to traditional antibiotics.