Controllably Biodegradable Hydroxyapatite Nanostructures for Cefazolin Delivery against Antibacterial Resistance

Abstract

Multidrug resistance (MDR) is a global threat posed by continuously evolving microbial resistance against currently available antimicrobial agents. In this study, we synthesized hydroxyapatite-based porous nanocarriers with pH-dependent biodegradation, using cefazolin (CFZ) as cargo drug against MDR E. coli, S. aureus, and P. aeruginosa. Oval-shaped porous hydroxyapatite nanoparticles (opHANPs) were synthesized via core-shell method. Field emission scanning electron microscopy revealed that the average length and width of opHANPs were found to be similar to 90 and similar to 110 nm, respectively with monodispersed size and morphology. The encapsulation efficiency (EE) of CFZ was observed to be dependent on the initial concentration of the drug (EE, 41.37-92.40% with 300-2000 mu g/mL of CFZ). Brunauer-Emmett-Teller specific surface area and pore width of opHANPs were 166.73 m(2)/g and 3.3 nm, respectively, indicating hierarchal pore distribution. The pH-responsive drug release was observed from CFZ-loaded opHANPs (CFZ@opHANPs). An enhanced drug-releasing behavior was observed at lower pH (4.5, 2.5, and 1.5). The study of release kinetics revealed that at pH 7.4, drug release is due to anomalous diffusion, while at lower pH, the drug release followed fickian diffusion model. Cytotoxic and hemolytic studies showed biocompatibility of CFZ@opHANPs with HepG2 and red blood cells. The growth kinetic study and colony-forming unit assay showed the superior antibacterial potential of CFZ@opHANPs, in contrast to carrier or CFZ alone, against MDR E. coli, S. aureus, and P. aeruginosa strains.