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Amphiphilic Cargo‐Loaded Nanocarrier Enhances Antibiotic Uptake and Perturbs Efflux: Effective Synergy for Mitigation of Methicillin‐Resistant Staphylococcus aureus
Author(s) -
Thiyagarajan Durairaj,
Das Gopal,
Ramesh Aiyagari
Publication year - 2017
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201700260
Subject(s) - nanocarriers , efflux , microbiology and biotechnology , staphylococcus aureus , antibiotics , ciprofloxacin , chemistry , biofilm , gentamicin , methicillin resistant staphylococcus aureus , adjuvant , pharmacology , bacteria , drug delivery , biology , biochemistry , immunology , genetics , organic chemistry
A pyridinium‐amphiphile‐loaded poly(lactic‐co‐glycolic acid) (PLGA) nanocarrier (C1‐PNC) was developed as an adjuvant in order to break the resistance and restore the susceptibility of methicillin‐resistant Staphylococcus aureus (MRSA) cells to therapeutic antibiotics. Notably, against a clinical MRSA strain, C1‐PNC was found to render 8‐ and 6‐fold decreases in the minimum biofilm eradication concentration (MBEC 90 ) of gentamicin and ciprofloxacin, respectively. Mechanistic studies on MRSA planktonic cells revealed that in the case of gentamicin, C1‐PNC promotes enhanced cellular uptake of the antibiotic, whereas the propensity of C1‐PNC to inhibit efflux pump activity could be leveraged to enhance cellular accumulation of ciprofloxacin, leading to effective killing of MRSA cells. Interestingly, the combinatorial dosing regimen of C1‐PNC and the antibiotics was nontoxic to cultured HEK293 cells. This nontoxic amphiphile‐loaded nanomaterial holds considerable promise as an adjuvant for antibiotic‐mediated alleviation of MRSA biofilms.