Tunable sequential drug delivery system based on chitosan/hyaluronic acid hydrogels and PLGA microspheres for management of non-healing infected wounds.

Treatment of non-healing infected wounds is an arduous task in clinical practice. Early antibacterial strategy and subsequent promotion of granulation tissue growth facilitate to cure the wounds. For this purpose, we fabricated a sequential drug delivery system by incorporation of an injectable hydrogel with porous PLGA microspheres. Vancomycin was linked to the injectable hydrogel via the reversible Schiff's base reaction, and VEGF were encapsulated into PLGA microspheres. After adding vancomycin, the strength and elasticity of the hydrogel were improved, and the gelation time was shortened. The results also demonstrated that the releasing profile of vancomycin was pH-dependent and the VEGF's profile was adjustable by changing the pore sizes of PLGA microspheres. The duration of VEGF release was longer than vancomycin. This hybrid system was valid to inhibit bacteria growth and accelerate vein endothelial cell proliferation in vitro. In rat models, it was effective to manage non-healing infected wounds by reducing inflammation and promoting angiogenesis. In conclusion, this sequential delivery system is promoting to manage non-healing infected wounds, and also provides a new thought to realize the staged drug release.