Prophylaxis of Arthroplasty-related Gram-negative Infections: Efficacy of Levofloxacin-loaded Sol–gel coatings
摘要
Orthopedic implant-associated infections (IAIs) remain a major clinical challenge, particularly those caused by Gram-negative bacteria (GNB) due to their high virulence and increasing antibiotic resistance. Conventional treatments, including surgery and systemic antibiotics, are often insufficient due to limited antibiotic penetration into infected tissues. As a result, local antibiotic delivery systems have emerged as promising alternatives. Among them, sol–gel coatings offer a versatile platform thanks to their tunable organic-inorganic hybrid structure, enabling controlled degradation and drug release. This study reports the development and characterization of levofloxacin-loaded sol–gel coatings designed for prophylaxis against GNB-related IAIs. Three formulations with increasing levofloxacin content (SG-LEV2L, SG-LEV4M, and SG-LEV5H) were synthesized and applied to titanium substrates. Coatings were evaluated for chemical composition, surface morphology, degradation behavior, release kinetics, and antibacterial efficacy. FT-IR and 29Si-NMR analyses confirmed the formation of a highly crosslinked polysiloxane network, with minor changes attributable to antibiotic incorporation. Surface analysis via SEM and AFM revealed uniform nanoporous surfaces, while adhesion tests demonstrated strong substrate bonding. Electrochemical impedance spectroscopy indicated stable degradation behavior with slight permeability differences among formulations. Drug release studies revealed a biphasic release pattern characterized by an initial near-constant release phase lasting 24 h, followed by a slower, diffusion-controlled phase. Mathematical modeling supported a diffusion-dominated mechanism, with evidence of anomalous transport in lower drug-load systems and Fickian diffusion in the high-load formulation. SG-LEV5H achieved a sustained release rate of 1.15 µg/h over the initial 24 h. Biofilm inhibition assays demonstrated near-complete elimination of sessile E. coli and up to 96.93% reduction in P. aeruginosa colonization. These findings highlight the potential of levofloxacin-loaded sol–gel-based coatings for delivering sustained drug release, strong adhesion to titanium, and effective inhibition of Gram-negative biofilm formation, supporting their potential use in the prophylaxis of orthopedic implant-associated infections.
Graphical Abstract