Project Summary: In cystic fibrosis (CF), treatment is difficult because chronic lung infections lead to biofilm formation and drug-resistant bacterial strains prevent antibiotics from working effectively. Antibiotic approaches specifically designed to address infections in the lung include inhaled antibiotics; however, resistant strains are a significant challenge. For delivery, such inhaled drugs must be formulated within a specified size range. Too large and they do not remain suspended to reach deep within the lungs. Too small and they remain in the air and are simply exhaled without embedding. Our scientific premise is that individual magnetic particles of this optimal size range can be inhaled into the lungs and subsequently assembled in place in the form of wheel-like assemblies, or ?wheels, to travel deep down lung pathways and disrupt mucus layers to enhance drug-induced biofilm removal. As both ?wheel assembly and driving forces are provided by an external magnetic field, once the procedure is finished, devices ?self- disassemble? into small building blocks removable by the body's natural mechanism for removal of dust and other foreign particles in the mucus lining. Our aims include: Aim 1: Identify applied magnetic field conditions that promote ?wheel-enhanced biofilm degradation. We will study model P. aeruginosa and CF patient-derived biofilms, with and without artificial sputum, and attach antibiotics or dispersal agents onto the magnetic particle surface and within tortuous microenvironments. We will also use nanoparticle-decorated ?wheels to perforate and penetrate the film and test with antibiotic/dispersal agent in solution. Aim 2: Determine conditions that support airborne delivery and transport of ?wheels in 3D environments. We will demonstrate airborne delivery of ?wheels and translation within 3D models of patient respiratory systems, with and without artificial sputum.

R21AI138214

2018-11-23

2021-10-31