Development of a Novel Nanostructured Hydroxyapatite for Antibiotic Delivery

Nanoscale hydroxyapatite (nHA) materials have been used in orthopaedics for over two decades, yet their potential for localised drug delivery remains underexplored. Commercial materials such as ReproBone® novo offer osteostimulative and injectable properties but lack antimicrobial effects, necessitating alternative infection treatments. This study aimed to develop an antibiotic-loaded nHA paste for targeted antibiotic release.
Gentamicin sulphate compared to other commonly used antibiotics demonstrated the highest efficacy against osteomyelitis-associated pathogens, retaining antibacterial activity after γ-irradiation (25 kGy). However, its release from nHA pastes (GTnHA) was hindered by electrostatic interactions at low concentrations (1 mg/mL). Higher concentrations (10 mg/mL, 44 mg/mL) allowed sustained release and confirmed antimicrobial activity, though mild cytotoxicity was observed in MC3T3-E1 and MG63 cells.
To enhance biocompatibility, nHA was surface-modified using 12-aminododecanoic acid (AD), producing positively charged amine-modified particles (nHA_AD), verified via zeta-potential and ninhydrin assays. nHA_AD exhibited improved cytocompatibility with no toxic effects. Incorporating gentamicin at 1 mg/mL (GTAD_1) and 10 mg/mL (GTAD_10) into AD-modified pastes (GTAD) resulted in significantly higher antibiotic release within 4 hours compared to GTnHA. Antibacterial assays demonstrated enhanced inhibition zones and greater bacterial log reduction, with GTAD_10 achieving complete bacterial eradication within 24 hours.
In vitro studies confirmed GTAD pastes were not highly cytotoxic at relevant concentrations. While GTAD_10 showed mild cytotoxicity (50% viability), MC3T3-E1 cells exhibited slightly greater sensitivity. These findings highlight the potential of surface-modified nHA pastes for antibiotic delivery, balancing antimicrobial efficacy with biocompatibility.
The development of this novel antibiotic-eluting nHA paste offers benefits for surgeons due to ease of use, improved patient outcomes, and reduced antibiotic resistance risks, making it a promising option for treating orthopaedic infections.