doi:10.2217/nnm-2019-0371engLacoma, AliciaUsón, LauraMendoza, GraciaSebastián, VíctorGarcia-Garcia, EstherMuriel-Moreno, BeatrizDomínguez, JoséArruebo, ManuelPrat, CristinaNovel intracellular antibiotic delivery system against Staphylococcus aureus: Cloxacillin-loaded poly(d, l-lactide-co-glycolide) acid nanoparticlesART-2020-118681Aim: 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.2020http://zaguan.unizar.es/record/15657510.2217/nnm-2019-0371http://zaguan.unizar.es/record/156575oai:zaguan.unizar.es:156575info:eu-repo/grantAgreement/EUR/ERC-2013-CoG-614715-NANOHEDONISMinfo:eu-repo/grantAgreement/ES/ISCIII/FEDER/PI17-01139info:eu-repo/grantAgreement/ES/MICINN/CTQ2017-84473-RNanomedicine 15, 12 (2020), 1189-1203byhttps://creativecommons.org/licenses/by/4.0/deed.esinfo:eu-repo/semantics/openAccess