Anti-staphylococcal Activity of Injectable Nano Tigecycline/Chitosan-PRP Composite Hydrogel Using Drosophila melanogaster Model for Infectious Wounds

Compared to the current treatment modalities, the use of an injectable hydrogel system, loaded with antibiotic encapsulated nanoparticles for the purpose of treating Staphylococcus aureus (S. aureus) chronic wound infections have several advantages. These include adhesiveness to infection site, reduced frequency of dressings, sustained drug release, inhibition of bacterial growth, and increased healing. In the present work tigecycline nanoparticles were loaded into chitosan platelet-rich plasma (PRP) hydrogel. The tigecycline nano particles (95 +/- 13 nm) were synthesized through ionic cross-linking method using chitosan, tripolyphosphate, and tigecycline and characterized by dynamic light scattering (DLS), scanning electron microscope (SEM), and Fourier transform infrared spectroscopy (FTIR). The synthesized nanoparticles and activated PRP powder were mixed with chitosan hydrogel to form a homogeneous gel. Rheology studies have confirmed the shear thinning property, thermal stability, and injectability of the prepared gel systems. The gel system was further assessed for its drug release property and found that it was released in a sustained manner. Hemolysis and blood-clotting assays demonstrated that the gel system was neither a hemolysin nor a hamper to the clotting cascade. Cell viability results showed that these nanoparticles were cyto-compatible. The bioactivity of PRP loaded chitosan gel toward fibroblast cell line was studied using cell proliferation and migration assay. In vitro antibacterial studies revealed that the gel system inhibited bacterial growth to a great extent. The antibacterial activity was further analyzed using ex vivo porcine skin assay. In vivo anti-Staphylococcal activity of the prepared hydrogels was studied using a Drosophila melanogaster infection model. The tigecycline and tigecycline nanoparticle incorporated chitosan gel showed a significant antibacterial activity against S. aureus. Thus, the gel system is an effective medium for antibiotic delivery and can be applied on the infection sites to effectively forestall various skin infections caused by S. aureus.