PROJECT SUMMARY. In this study, we will develop a novel ion current-based iontophoresis device that can safely apply high intensity currents to deliver a therapeutically effective concentration of antibiotics into biofilms within a short period of time to achieve efficacious eradication of chronic wound biofilm infections. Chronic wounds are currently affecting more than 6 million people in the US. More than 78% of chronic wounds have biofilms, which arrest the wounds in a prolonged inflammatory phase and prevent wound healing. Biofilms are difficult to treat, because biofilm bacteria are more resistant to antibiotics and a protective matrix of extracellular polymeric substances reduce the diffusion rate of antibiotics into biofilms. As a result, current antibiotic delivery technologies are not capable of delivering sufficient antibiotic concentrations to effectively eradicate chronic wound biofilm infections. Iontophoresis is a non-invasive, electrical current-based drug delivery technology. Conventional iontophoresis devices have low antibiotic delivery efficiency due to the low current intensities they use. Although higher current intensities increase antibiotic delivery efficiency, they can cause significant tissue burn due to the temperature increase and the pH changes at the device/tissue interface. In this proposal, based on an ion current-conducting hydrogel ionic circuit (HIC) invented in our lab, we aim to develop a novel iontophoresis device that can safely apply current intensities that are significantly higher than what current iontophoresis devices use. Higher current intensities will allow us to deliver significantly higher amount of antibiotics to efficaciously eliminate biofilm bacteria and restore the normal wound healing process. In Specific Aim 1, we will first design and optimize an HIC-based, skin-mountable iontophoretic antibiotic delivery device through computer-aided finite-element simulation. We will then determine the antibiotic delivery efficiency and biofilm eradication efficacy of our device using an excised human skin-based wound infection model. The safety of high-intensity ion current application will also be evaluated using in vitro cell cultures and healthy rats. In Specific Aim 2, we will determine the in vivo biofilm eradication efficacy and wound healing enhancement efficacy of our device using a rat bipedicled skin flap-based ischemic wound infection model. Our outcome will establish an optimal device design and a critical proof-of-concept for the in vivo safety, biofilm eradication efficacy, and chronic wound healing enhancement efficacy of our high-intensity iontophoretic antibiotic delivery device. The enhanced healing of chronic wounds enabled by our device will greatly improve the quality of life for patients and reduce the overall healthcare cost.

PROJECT NARRATIVE The proposed research is relevant to public health because it will develop a novel, highly efficacious antibiotic delivery technology to combat chronic wound biofilm infections. This project is relevant to NIAMS’s mission by developing transformative technology with potential to enhance chronic wound healing.