Polymer therapeutics for effective antimicrobial targeting in burn injury

Abstract

Gram-negative infection is a leading cause of mortality. Antimicrobial development has been outpaced by Gram-negative multi-drug resistance. While older antibiotics such as colistin remain effective, their use is extremely limited by their inherent nephro/neurotoxicity. Novel methods for safe and effective delivery would, therefore, radically improve patient treatment. Polymer therapeutics are nanomedicines allowing custom-engineered targeted optimal drug delivery through conjugation with a water-soluble polymer. The newmacromolecule would benefit from passive targeting through the Enhanced Permeability and Retention effect. Conjugation would mask in-transit toxicity. Degradation of dextrin by α-amylase at the infected site would unmask colistin reinstating its antimicrobial activity. This study aims to develop the first fully customisable library of bioresponsive dextrin-colistin conjugates for safe and effective antimicrobial delivery in infection.