Natural bone-mimicking hydroxyapatite nanoplates as a novel antibiotic drug vehicle: A comparative study with nanorods

Developing a biocompatible drug vehicle with controlled release is vital for safe and sustained antibiotic delivery at infection site to ensure complete bacterial eradication without systemic toxicity. Hydroxyapatite (HA) nanocrystals (NCs), naturally found in living bone as nanoplates (NPTs), offer exceptional biocompatibility and efficient drug binding sites. However, research on antibiotic loading in HA NPTs and their release behavior for controlling bacterial growth is still scarce. Therefore, the present study focuses on antibacterial effect of doxycycline hyclate (DOX)-loaded HA NPTs and thin NPTs (TNPTs) with detailed analyses of their drug loading efficiency and release profile, compared to HA nanorods (NRs). HA NCs, including NRs, NPTs, and TNPTs were synthesized using polyvinyl alcohol (PVA) as a shape-controlling agent via hydrothermal method. The DOX loading efficiencies of HA NRs, NPTs, and TNPTs were determined to be 45.5, 62.2, and 73.3 %, respectively, confirmed using Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and electron microscopies. Among the tested HA morphologies, HA TNPTs exhibited the most sustained DOX release profile, followed by HA NPTs and NRs. The differential DOX loading and release rate was explained through surface area of HA and their nature of interaction with DOX. In vitro cell culture studies demonstrated that all DOX-HA NCs effectively promoted cell adhesion, proliferation, and good hemocompatibility. Further, the antibacterial activity of DOX-HA NCs was examined using both, quantitative (MTT assay) and qualitative (Live-dead and colony-counting) experiments against S. aureus bacteria. It is found that unlike free DOX, the prolonged DOX release from HA TNPTs leads to nearly complete inhibition of bacterial growth at 200 μg/ml against the similar bacteria, highlighting their potential as an effective antibiotic vehicle for bacterial eradication.