In situ precipitated hydroxyapatite-chitosan composite loaded with ciprofloxacin: Formulation, mechanical, in vitro antibiotic uptake, release, and antibacterial properties

Abstract

Three-dimensional hydroxyapatite-chitosan (HA-CS) composites loaded with ciprofloxacin antibiotic (HA–CS–CIP) were formulated using the in situ and the solid-liquid method coupled with the freeze-drying process. The interaction of the HA-CS composite powder and ciprofloxacin antibiotic (CIP) was investigated by batch adsorption essays. The kinetic and the isotherm data were fitted well to the pseudo-second-order and Freundlich models, respectively. The compressive strength of the HA-CS composite was increased by 7-fold and 10-fold when using respectively 15 wt% and 30 wt% of the polymer compared to the HA-CS5 formulation (3.6 ± 0.7 MPa) made only from HA powder and CS gel (5 wt%). However, this parameter decreased from 36.8 ± 8.5 MPa down to 20.5 ± 4.7 MPa when the antibiotic content increased from 0 up to 9 wt%, respectively. The in vitro release results showed a sustained and controlled CIP release for up to 10 days. The release data fitting and modeling indicate that the process follows a Fickian diffusion mechanism. Also, the formulated composite revealed an antibacterial effect against Staphylococcus aureus and Escherichia coli bacteria. The developed composite may be a promising candidate for bone substitution and as an antibiotic local delivery system for the treatment of orthopedic implant-associated infections.