Functionalised liposomal formulations for delivery of antibiotic agents

Abstract

Antimicrobial resistance is a major global healthcare challenge. Beyond the discovery of novel antimicrobial agents, the development of novel formulations for enhancing current antibiotics is a promising strategy to reduce the rate of treatment failure. Drug delivery nano-carriers can achieve high local concentration of antimicrobial agents, reduce toxicity, and improve biodistribution and pharmacokinetics. We have taken two approaches to enhance antibiotic delivery and effectiveness. Firstly, we used a bespoke targeted liposomal system for intracellular antibiotic delivery to phagocytic cells. This enables treatment of an intracellular Gram-negative infection with a cell-impermeable antibiotic. Targeted liposomes were found to significantly enhance uptake compared to uncoated liposome control formulations both in in vitro and in vivo (zebrafish model). Secondly, liposomal nanoformulations were utilised to deliver peptide antibiotics, where liposomes protect peptides from degradation, and allow potential co-delivery of combination therapeutics. We investigated different liposomal formulations and drug combinations against E. coli and S. aureus. We show that peptide-loaded liposomes are more efficient compared to free drug in inhibiting the growth of both Gram-negative and Gram-positive bacteria. These initial results suggest that liposome-mediated delivery can be utilised for the repositioning and repurposing of existing antibiotics, potentially allowing for the treatment of diverse infections in a more effective manner.