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

An injectable osteoconductive polyelectrolyte complex (PEC)-hydroxyapatite (HAP) formulation capable of controlled delivery of ciprofloxacin has been developed from a novel biodegradable PEC and antibiotic loaded nascent hydroxyapatite (n-HAP) for the treatment of osteomyelitis. A single source (chitosan) derived polyelectrolytes were complexedin situin 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 byin vitrobiomineralization 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 againstS. aureusandE. 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.