Optimized solid lipid nanoparticles for co-delivery of gentamicin and doxycycline: a novel approach to combat intracellular brucella abortus infections

Abstract

This study evaluates the potential of gentamicin (GEN) and doxycycline (DOX) co-loaded solid lipid nanoparticles (SLNs) for treating Brucella abortus infections. Optimized SLN formulations demonstrated mean particle sizes of 211.2 ± 10.8 nm, a polydispersity index of 0.42 ± 0.019, encapsulation efficiency of 95.3 ± 1.2%, and loading efficiency of 14.7 ± 0.1%. Drug release profiles revealed a biphasic release, achieving 91.1% and 73% cumulative release for GEN and DOX, respectively, over 72 h. In vitro studies on J774.A1 macrophages indicated significantly enhanced antibacterial activity and reduced cytotoxicity for SLN-GEN/DOX, achieving a minimum inhibitory concentration of 1.25 µg/mL and reducing intracellular bacterial load to 3.7 ± 0.02 Log₁₀ colony forming unit (CFU). In vivo, SLN-GEN/DOX-treated mice exhibited superior bacterial clearance, with spleen bacterial counts of 1.4 ± 0.03 Log₁₀ CFU compared to 2.4 ± 0.06 Log₁₀ CFU for the free drug combination. Additionally, reduced systemic toxicity was observed, with ALT and AST levels of 42.3 ± 1.2 U/mL and 64.1 ± 1.6 U/mL, respectively. These findings suggest that SLN-GEN/DOX offers a promising therapeutic approach for brucellosis by improving drug stability, bioavailability, and efficacy while minimizing systemic toxicity. Further studies should focus on clinical applications and mechanistic insights into SLN-mediated drug delivery.

Keywords: Brucella abortus; Co-drug delivery; Doxycycline; Gentamicin; Solid lipid nanoparticles.