Novel Intracellular Antibiotic Delivery System Against <i>Staphylococcus Aureus</i> : Cloxacillin-Loaded Poly( <scp>D</scp> , <scp>L</scp> -Lactide-Co-Glycolide) Acid Nanoparticles
Alícia Lacoma, Laura Usón, Gracia Mendoza, Víctor Sebastián, Esther García-García, Beatriz Muriel-Moreno, José Domínguez, Manuel Arruebo, Cristina Prat
Abstract
Aim: First, to compare in vitro minimum inhibitory concentrations (MIC) of free cloxacillin and cloxacillin-containing nanoparticles (NP) against methicillin-susceptible (MSSA) and resistant Staphylococcus aureus (MRSA) and second, to assess NP antimicrobial activity against intracellular S. aureus. Methods: Poly(d,l-lactide-co-glycolide) acid (PLGA)-NP were loaded with cloxacillin and physico-chemically characterized. MICs were determined for reference strains Newman-(MSSA) and USA300-(MRSA). Murine alveolar macrophages were infected, and bacterial intracellular survival was assessed after incubating with free-cloxacillin or PLGA-cloxacillin-NP. Results & conclusion: For both isolates, MICs for antibiotic-loaded-NP were lower than those obtained with free cloxacillin, indicating that the drug encapsulation improves antimicrobial activity. A sustained antibiotic release was demonstrated when using the PLGA-cloxacillin-NP. When considering the lowest concentrations, the use of drug-loaded NP enabled a higher reduction of intracellular bacterial load.