2023 AIChE Annual Meeting
Development of ?-Lactamase Responsive Microneedles for Treatment of Diabetic Foot Ulcer Bacterial Biofilm Infections
Diabetic foot ulcers (DFUs) often lead to infections, with 60% of those infections associated with biofilm formation. Biofilms represent three-dimensional microbial communities embedded within a matrix of extracellular polymeric substances (EPS). Bacterial biofilms exhibit various antibiotic-resistant mechanisms, including the production of β-lactamases (βLs), which inactivate many common β-lactam antibiotics via hydrolysis. The EPS barrier limits the effectiveness of current topical and systemic treatments, diminishing the efficacy of traditional topical and systemic treatments, thus elevating the risk of antibiotic resistance. A novel antibiotic-loaded microneedle (MN) patch offers an alternative to biofilm infection treatments by using miniaturized needles (<1 mm in height) to puncture the EPS, releasing an antibacterial cargo into the biofilm. To overcome antibiotic resistance, we developed a βL-responsive MN patch containing a βL-responsive crosslinker that can undergo free radical photopolymerization and degrade in the presence of βLs. The MNs will be compared to a non-responsive formulation using poly(ethylene glycol) diacrylate as the crosslinker. To assess the mechanical stability, compression testing and in vitro puncture studies were conducted with non-responsive MNs formulated with and without fluorescent nanoparticles as a drug cargo model. At a pre-load of 0.1 N, the compression testing results indicated an exponential increase in compression force at a displacement of ~0.3 mm of the non-responsive MNs. Puncture studies indicated that non-responsive MNs punctured through 2 parafilm layers, with a 47% decrease in holes created between the first and second layers. Visual confirmation of MN formation and its deformation under mechanical stress was provided by scanning electron microscopy and confocal microscopy. Current work is using similar approaches to characterize the βL-responsive MNs.