Polymeric bisphosphonate derivative of ciprofloxacin – synthesis, structural analysis and antibacterial activity of the prospective conjugate

Abstract

Infections associated with biometrics represent a significant challenge to the most widespread medical applications. In this study, new macromolecular conjugates containing ciprofloxacin (CIP) and the bisphosphonate (BP) molecules were synthesized. Polymeric matrices (disyndiotactic and atactic polylactides, and poly(ε-caprolactone)) used in macromolecular conjugates synthesis were obtained in the presence of tin (II) 2-ethylhexanoate/phenylalanine catalytic system. The cyto- and genotoxicity of the synthesized polyesters were tested. It was found that the kinetic release of bisphosphonate derivative of ciprofloxacin (BP-CIP) from the obtained macromolecular conjugates tested in vitro at pH 7.4, was strongly dependent on the the polyester chain microstructure. Importantly, in some cases, the kinetics of the BP-CIP release was nearly zero-order. The microbiological activity of new drug delivery systems was determined. The preliminary results show that the new macromolecular conjugates, which contain CIP and BP, are prospective and can be potentially applied in the technology of ’long-term‘implantation drug delivery systems.

GRAPHICAL ABSTRACT

KEYWORDS:

• Biodegradable biomedical polyesters
• bisphosphonate
• macromolecular conjugates
• ciprofloxacin
• drug delivery systems

Additional information

Funding

This work was supported by the research program (Project NCN DEC-2011/03/D/ST5/05793: ‘Synthesis and characterization of polymer-apatite composite containing selenium and bisphosphonates’) of the National Science Center Poland.