The emergence of drug-resistance among pathogenic bacteria constitutes one of the paramount challenges to the human heath worldwide. This threat is further exacerbated by biofilm-associated infections that are even more challenging to treat. Conventional antibiotic-therapies are ineffective due to their inability to penetrate biofilm matrix coupled with the rapidly growing number of antibiotic-resistant strains. Host-defence peptide mimicking synthetic polymeric have emerged as promising novel antimicrobials that can disrupt the microbial membrane and readily penetrate biofilm matrix. However, their lack of specificity towards mammalian hosts limits their widespread therapeutic application. Here, we report synergistic antimicrobial therapy using engineered polymeric nanoparticles with colistin antibiotic for combating MDR bacterial and biofilm infections. We observed an 8-16-fold decrease in antibiotic dosage in presence of polymeric nanoparticles to combat planktonic cells and eradicate pre-formed biofilms of multiple MDR species. The synergy observed on planktonic bacteria was attributed to the ability of NPs (at sub-lethal concentrations) to create small pores on bacterial membrane that increased influx of antibiotics inside the microbes. Moreover, antibiotic accumulation inside biofilms increased by ~3.5 times in presence of NPs, resulting in a synergistic effect to kill the constituent microbes. Overall, this strategy demonstrates the ability of polymeric NPs to minimize the side-effects caused by high doses of ‘lethal’ antibiotics while simultaneously rejuvenating the antibiotics rendered ineffective due to development of drug-resistance in bacteria.

Combination therapy using polymeric nanoparticles with colistin antibiotic for the treatment of bacterial and biofilm infections

256th National Meeting (2018)

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