TY - JOUR
T1 - Novel intracellular antibiotic delivery system against Staphylococcus aureus
T2 - Cloxacillin-loaded poly(d,l-lactide-co-glycolide) acid nanoparticles
AU - Lacoma, Alicia
AU - Usón, Laura
AU - Mendoza, Gracia
AU - Sebastián, Victor
AU - Garcia-Garcia, Esther
AU - Muriel-Moreno, Beatriz
AU - Domínguez, Jose
AU - Arruebo, Manuel
AU - Prat, Cristina
N1 - Funding Information:
This project was funded jointly by SEPAR (Spanish Society for Pneumology and Thoracic Surgery), CIBER-BBN and CIBERES (Spanish Consortia for Research on Bioengineering, Biomaterials and Nanomedicine, and on Respiratory Diseases, respectively). This research was also supported by the Instituto de Salud Carlos III (PI 17/01139), integrated in the Plan Nacional de I+D+I and co-funded jointly by the ISCIII Subdirecció n General de Evaluació n and the Fondo Europeo de Desarrollo Regional (FEDER). We also thank the support from The Spanish Ministry of Science, Innovation and Universities (grant: CTQ2017-84473-R). We also acknowledge financial support from the EU (ERC Consolidator grant program, ERC-2013-CoG-614715, NANOHEDONISM). J Doḿinguez and G Mendoza are researchers from the Miguel Servet Program. C Prat was awarded by Programa Germans Trias Sapiens-Fundació Catalunya la Pedrera and European Respiratory Society - ERS Short-Term Research Fellowship 2018 (STRTF201810-00467). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Funding Information:
This project was funded jointly by SEPAR (Spanish Society for Pneumology and Thoracic Surgery), CIBER-BBN and CIBERES (Spanish Consortia for Research on Bioengineering, Biomaterials and Nanomedicine, and on Respiratory Diseases, respectively). This research was also supported by the Instituto de Salud Carlos III (PI 17/01139), integrated in the Plan Nacional de I+D+I and co-funded jointly by the ISCIII Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER). We also thank the support from The Spanish Ministry of Science, Innovation and Universities (grant: CTQ2017-84473-R). We also acknowledge financial support from the EU (ERC Consolidator grant program, ERC-2013-CoG-614715, NANOHEDONISM). J Domínguez and G Mendoza are researchers from the Miguel Servet Program. C Prat was awarded by Programa Germans Trias Sapiens-Fundació Catalunya la Pedrera and European Respiratory Society – ERS Short-Term Research Fellowship 2018 (STRTF201810-00467). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.
Publisher Copyright:
© 2020 Alicia Lacoma and all co-authors.
PY - 2020/5
Y1 - 2020/5
N2 - 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.
AB - 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.
KW - antimicrobial
KW - drug delivery
KW - intracellular infection
KW - nanoparticle
KW - Staphylococcus aureus
UR - https://www.scopus.com/pages/publications/85085904551
U2 - 10.2217/nnm-2019-0371
DO - 10.2217/nnm-2019-0371
M3 - Article
C2 - 32370602
AN - SCOPUS:85085904551
SN - 1743-5889
VL - 15
SP - 1189
EP - 1203
JO - Nanomedicine
JF - Nanomedicine
IS - 12
ER -