Injectable polyelectrolyte complex-nascent HAP biodegradable antibiotic delivery system for the treatment of osteomyelitis.

An injectable osteoconductive polyelectrolyte complex -hydroxyapatite formulation capable of controlled delivery of ciprofloxacin has been developed from a novel biodegradable polyelectrolyte complex and antibiotic loaded nascent hydroxyapatite (n-HAP) for the treatment of osteomyelitis. A single source (chitosan) derived polyelectrolytes were complexed in situ in the presence of n-HAP, pre-loaded with ciprofloxacin. The PEC- (n-HAP) nanoformulation (HPEC) was characterized by FT-IR, XRD, TGA and TEM analyses. HPEC combines functionalities of n-HAP (crystallinity and osteoconductivity) as well as PEC (biodegradable hydrophilic electrostatically bound macromolecular network) imparting better control over swelling and degradation kinetics favourable for drug release and transport of micronutrients. MTT assay and cytoskeleton staining (MG 63 cells) established cytocompatibility of HPEC. Early biomimetic mineralization of apatite was manifested under simulated physiological condition with a Ca/P of 1.23 (day 3) and 1.55 (day 6) complimented by in vitro biomineralization of MG-63 and Human Osteosarcoma (HOS) cells in a week (Alizarin Red S staining), which was further validated by calcium quantification. Antibacterial efficacy of HPEC has been evaluated by delivery kinetics of ciprofloxacin and by disc diffusion method against S. aureus and E. coli. The injectable system therefore possesses unique combination of functionalities: osteoconduction enriched with early biomineralization, antibacterial activity and is biodegradable; hence highly suitable for osteomyelitis treatment.