Preparation and characterization of tildipirosin-loaded solid lipid nanoparticles for the treatment of intracellular Staphylococcus aureus infections†

Abstract

To enhance the antibacterial efficacy of tildipirosin against Staphylococcus aureus (S.A.) infections, optimized solid lipid nanoparticles loaded with tildipirosin (SLN-TD) were developed, using docosanoic acid (DA), octadecanoic acid (OA), hexadecanoic acid (HA), and tetradecanoic acid (TA) as lipid components. The efficacy of these nanoparticles against S.A. was evaluated using orthogonal design analysis. FTIR, DLS, HPLC, and TEM analyses confirmed that tildipirosin was successfully incorporated into the solid lipid nanoparticles, resulting in an optimal nanoparticle drug delivery system with a particle size of 322.63 ± 1.51 nm, a zeta potential of 37.83 ± 0.95 mV, an encapsulation efficiency of 82.23 ± 0.45%, and a drug loading capacity of 7.36 ± 0.18%. The SLN-TD system exhibited high stability, effective sustained release in vitro, and enhanced intracellular activity against S.A. Pharmacokinetic studies in rats administered 4 mg kg⁻¹via intramuscular and oral routes showed that, compared to unencapsulated tildipirosin (TD), SLN-TD provided sustained release in vivo and improved gastrointestinal absorption with higher bioavailability. Additionally, in a mouse model of S.A. infection, SLN-TD demonstrated superior antibacterial activity and sustained drug delivery for effective treatment. This study offers a promising multifunctional nanoparticle drug delivery system for the effective treatment of S.A. infections and enhances the oral bioavailability of tildipirosin, with potential applications in veterinary medicine.