Antimicrobial Zn2+-Carboxymethyl Chitosan Cryogel for Controlled Loading and Release of Ciprofloxacin via Coordination Bonds

The local application of broad-spectrum antibiotics via polymeric drug delivery systems is a promising alternative to their systemic administration in wound healing, prevention and treatment of infections associated with surgical implants. However, low and poorly controlled loading efficiency and 100% burst release are common problems for the materials with weak physical interaction between antibiotics and polymeric matrices. Here, we report a new multifunctional carboxymethyl chitosan (CMC) cryogel, which efficiently prevents bacterial adhesion to the surface, kills bacteria in the solution via controlled release of ciprofloxacin (CIP), and promotes fibroblast proliferation. The suggested approach is based on CIP loading to Zn²⁺-chelated CMC cryogel via the ligand exchange reaction. We have shown that, due to the strong binding of Zn²⁺ to CMC, the antibacterial effect and toxicity to fibroblasts of CMC-Zn-CIP cryogels were mainly determined by the content of loaded CIP, which can be precisely controlled via Zn²⁺ content in cryogel. CMC cryogels containing 20 mgZn/g can be loaded with CIP amounts sufficient to completely suppress the growth of hospital strain <i>Klebsiella oxytoca</i> with MIC of 0.125 µg/mL, while maintaining a fibroblast viability at the level of 85-90%.