Microneedles: Bypassing the Gastrointestinal Microbiota to Circumvent Antibiotic Resistance (360G-Wellcome-206854_Z_17_Z)

We will validate a novel antibiotic delivery strategy which overcomes development of resistance, thus extending the lifespan of existing antibiotics. It will reduce deleterious effects on indigenous microbiomes by minimising exposure of the gut microbiome (a major reservoir of antimicrobial resistance). Importantly, it will also permit at-home delivery of new antibiotics that would otherwise require in-patient administration. Our key questions are: Q1 How do we optimise novel microneedle systems for transdermal delivery of clinically-effective antibiotic doses? Q2 Does microneedle delivery prevent exposure of the gut microbiome to antibiotics and avoid disruption of this community? Q3 Does microneedle delivery reduce/prevent emergence of resistance in key opportunistic pathogens which are normal residents of the human gut microbiome? Q4 Does microneedle delivery avoid selection of resistant strains from outside the gut microbiome and their incorporation into the gut microbiome? Q5 Can microneedle delivery treat infection as successfully as conventional orally- or intravenously-administered antibiotics? We will: Formulate microneedle systems containing model antibiotics Illustrate in vitro and in vivo transdermal delivery Demonstrate avoidance of gut microbiome exposure and resistance-sparing capabilities in vivo relative to oral delivery Show efficacy of transdermally-delivered antibiotics against microbial infections in vivo