Jump to main content
Jump to site search

Micellar Chemotherapeutic Platform Based on a Bifunctional Salicaldehyde Amphiphile Delivers a "Combo-Effect" for Heightened Killing of MRSA


The devastating infections caused by methicillin-resistant Staphylococcus aureus (MRSA) coupled with their high resistance towards antibiotics underscores the need of an effective anti-MRSA therapeutic. The present study illustrates the use of a salicaldehyde based bactericidal amphiphile (C1) in generating a micellar carrier that renders delivery of therapeutic antibiotics. The inherent membrane-targeting activity of C1 present in the micelle could be leveraged to counter the resistance of MRSA and enhance cellular uptake of the released antibiotics, resulting in effective elimination of the pathogen. The inherent bactericidal and antibiofilm activity of C1 was captured in FESEM analysis, solution-based assays and fluorescence microscopy. ANS-based fluorescence spectroscopy indicated that the critical micelle concentration (CMC) for C1 was 18.5 µM in water. DLS studies and FESEM analysis indicated that the average particle size for micelles based on C1 (C1M) and rifampicin-loaded C1M (C1M-R) was smaller than vancomycin-loaded C1M (C1M-V). C1M-R and C1M-V rendered sustained release of the antibiotics in physiologically relevant fluids. Notably, following interaction with MRSA for 3 h, the relative anti-MRSA activity of C1M-R and C1M-V were nearly 12-fold and 8-fold higher, respectively, as compared to the free antibiotics at equivalent concentration, highlighting the merit of leveraging the activity of C1 and the antibiotic concurrently in the micellar system. The relative cell-free antibiotic was also manifold lower in case of C1M-R and C1M-V treated MRSA as against treatment with free antibiotics, suggesting that the amphiphilic warhead breached the membrane barrier and enhanced cellular uptake of the released antibiotics. Interestingly, C1M-R and C1M-V exhibited high therapeutic index, being non-toxic to HEK 293 cells at concentrations higher than their minimum inhibitory concentration (MIC) against MRSA and could be employed as an antibacterial coating to prevent MRSA biofilm formation on surgical silk sutures. The antibiotic-replete biocompatible micelles based on a self-assembling membrane-targeting amphiphile described herein represents a promising framework to integrate multiple warheads and generate a potent anti-MRSA therapeutic material.

Back to tab navigation

Supplementary files

Publication details

The article was received on 06 Dec 2017, accepted on 28 Feb 2018 and first published on 02 Mar 2018

Article type: Paper
DOI: 10.1039/C7TB03150E
Citation: J. Mater. Chem. B, 2018, Accepted Manuscript
  •   Request permissions

    Micellar Chemotherapeutic Platform Based on a Bifunctional Salicaldehyde Amphiphile Delivers a "Combo-Effect" for Heightened Killing of MRSA

    P. Dey, S. Mukherjee, G. Das and R. Aiyagari, J. Mater. Chem. B, 2018, Accepted Manuscript , DOI: 10.1039/C7TB03150E

Search articles by author