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dc.contributor.authorTan, Chuan Haoen_US
dc.contributor.authorJiang, Laien_US
dc.contributor.authorLi, Wenruien_US
dc.contributor.authorChan, Siew Herngen_US
dc.contributor.authorBaek, Jong-Suepen_US
dc.contributor.authorNg, Noele Kai Jingen_US
dc.contributor.authorSailov, Talgaten_US
dc.contributor.authorKharel, Sharaden_US
dc.contributor.authorChong, Kelvin Kian Longen_US
dc.contributor.authorLoo, Joachim Say Chyeen_US
dc.identifier.citationTan, C. H., Jiang, L., Li, W., Chan, S. H., Baek, J., Ng, N. K. J., Sailov, T., Kharel, S., Chong, K. K. L. & Loo, J. S. C. (2021). Lipid-polymer hybrid nanoparticles enhance the potency of ampicillin against Enterococcus faecalis in a protozoa infection model. ACS Infectious Diseases, 7(6), 1607-1618.
dc.description.abstractEnterococcus faecalis (E. faecalis) biofilms are implicated in endocarditis, urinary tract infections, and biliary tract infections. Coupled with E. faecalis internalization into host cells, this opportunistic pathogen poses great challenges to conventional antibiotic therapy. The inability of ampicillin (Amp) to eradicate bacteria hidden in biofilms and intracellular niches greatly reduces its efficacy against complicated E. faecalis infections. To enhance the potency of Amp against different forms of E. faecalis infections, Amp was loaded into Lipid-Polymer hybrid Nanoparticles (LPNs), a highly efficient nano delivery platform consisting of a unique combination of DOTAP lipid shell and PLGA polymeric core. The antibacterial activity of these nanoparticles (Amp-LPNs) was investigated in a protozoa infection model, achieving a much higher multiplicity of infection (MOI) compared with studies using animal phagocytes. A significant reduction of total E. faecalis was observed in all groups receiving 250 µg/mL Amp-LPNs compared with groups receiving the same concentration of free Amp during three different interventions, simulating acute and chronic infections and prophylaxis. In early intervention, no viable E. faecalis was observed after 3 h LPNs treatment whereas free Amp did not clear E. faecalis after 24 h treatment. Amp-LPNs also greatly enhanced the antibacterial activity of Amp at late intervention, and boosted the survival rate of protozoa approaching 400%, where no viable protozoa were identified in the free Amp groups at the 40 h post-infection treatment timepoint. Prophylactic effectiveness with Amp-LPNs at a concentration of 250 μg/mL was exhibited in both bacteria elimination and protozoa survival towards subsequent infections. Using protozoa as a surrogate model for animal phagocytes to study high MOI infections, this study suggests that LPN-formulated antibiotics hold the potential to significantly improve the therapeutic outcome in highly complicated bacterial infections.en_US
dc.description.sponsorshipAgri-Food and Veterinary Authority of Singapore (AVA)en_US
dc.description.sponsorshipMinistry of Education (MOE)en_US
dc.relationSingapore Centre for Environmental Life Sciences Engineering (SCELSE) (MOE/RCE: M4330019.C70)en_US
dc.relationMinistry of Education AcRF-Tier 1 grant (RG19/18)en_US
dc.relationAgri-Food & Veterinary Authority of Singapore (APF LCK102)en_US
dc.relationBiomedical Research Council (BMRC) - Therapeutics Development Review (TDR-G-004-001)en_US
dc.relationNTU-HSPH grant (NTU-HSPH 17002)en_US
dc.relationBill and Melinda Gates Foundation (OPP1199116)en_US
dc.relation.ispartofACS Infectious Diseasesen_US
dc.rightsThis document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Infectious Diseases, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see
dc.subjectScience::Biological sciences::Microbiology::Bacteriaen_US
dc.titleLipid-polymer hybrid nanoparticles enhance the potency of ampicillin against Enterococcus faecalis in a protozoa infection modelen_US
dc.typeJournal Articleen
dc.contributor.schoolSchool of Materials Science and Engineeringen_US
dc.contributor.organizationHarvard T.H. Chan School of Public Healthen_US
dc.contributor.researchNTU Institute for Health Technologiesen_US
dc.contributor.researchSingapore Centre for Environmental Life Sciences and Engineering (SCELSE)en_US
dc.description.versionAccepted versionen_US
dc.description.acknowledgementThe authors would like to acknowledge the financial support from the Singapore Centre for Environmental Life Sciences Engineering (SCELSE) (MOE/RCE: M4330019.C70), Ministry of Education AcRF-Tier 1 grant (RG19/18), Agri-Food & Veterinary Authority of Singapore (APF LCK102), Biomedical Research Council (BMRC) - Therapeutics Development Review (TDR-G-004-001), NTU-HSPH grant (NTU-HSPH 17002), and the Bill and Melinda Gates Foundation (OPP1199116).en_US
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