Antimicrobial Zn<sup>2+</sup>-Carboxymethyl Chitosan Cryogel for Controlled Loading and Release of Ciprofloxacin via Coordination Bonds
Svetlana Bratskaya,
Andrey Boroda,
Tamara Bogomaz,
Yuliya Privar,
Mariya Maiorova,
Daniil Malyshev,
Anastasiia Shindina,
Anna Skatova,
Roman Goncharuk
Affiliations
Svetlana Bratskaya
Institute of Chemistry, Far Eastern Branch of the Russian Academy of Sciences, 159, Prosp. 100-Letiya Vladivostoka, 690022 Vladivostok, Russia
Andrey Boroda
A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch of Russian Academy of Sciences, 17 Palchevskogo Street, 690041 Vladivostok, Russia
Tamara Bogomaz
School of Medicine and Life Sciences, Far Eastern Federal University, 10 Ajax Bay, Russky Island, 690922 Vladivostok, Russia
Yuliya Privar
Institute of Chemistry, Far Eastern Branch of the Russian Academy of Sciences, 159, Prosp. 100-Letiya Vladivostoka, 690022 Vladivostok, Russia
Mariya Maiorova
A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch of Russian Academy of Sciences, 17 Palchevskogo Street, 690041 Vladivostok, Russia
Daniil Malyshev
A.V. Zhirmunsky National Scientific Center of Marine Biology, Far Eastern Branch of Russian Academy of Sciences, 17 Palchevskogo Street, 690041 Vladivostok, Russia
Anastasiia Shindina
School of Medicine and Life Sciences, Far Eastern Federal University, 10 Ajax Bay, Russky Island, 690922 Vladivostok, Russia
Anna Skatova
Institute of Chemistry, Far Eastern Branch of the Russian Academy of Sciences, 159, Prosp. 100-Letiya Vladivostoka, 690022 Vladivostok, Russia
Roman Goncharuk
School of Medicine and Life Sciences, Far Eastern Federal University, 10 Ajax Bay, Russky Island, 690922 Vladivostok, Russia
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 Klebsiella oxytoca with MIC of 0.125 µg/mL, while maintaining a fibroblast viability at the level of 85–90%.
