Affinity interactions drive post-implantation drug filling, even in the presence of bacterial biofilm

摘要

Current post-operative standard of care for surgical procedures, including device implantations, dictates prophylactic antimicrobial therapy, but a percentage of patients still develop infections. Systemic antimicrobial therapy needed to treat such infections can lead to downstream tissue toxicities and generate drug-resistant bacteria. To overcome issues associated with systemic drug administration, a polymer incorporating specific drug affinity has been developed with the potential to be filled or refilled with antimicrobials, post-implantation, even in the presence of bacterial biofilm. This polymer can be used as an implant coating or stand-alone drug delivery device, and can be translated to a variety of applications, such as implanted or indwelling medical devices, and/or surgical site infections. The filling of empty affinity-based drug delivery polymer was analyzed in an in vitro filling/refilling model mimicking post-implantation tissue conditions. Filling in the absence of bacteria was compared to filling in the presence of bacterial biofilms of varying maturity to demonstrate proof-of-concept necessary prior to in vivo experiments. Antibiotic filling into biofilm-coated affinity polymers was comparable to drug filling seen in same affinity polymers without biofilm demonstrating that affinity polymers retain ability to fill with antibiotic even in the presence of biofilm. Additionally, post-implantation filled antibiotics showed sustained bactericidal activity in a zone of inhibition assay demonstrating post-implantation capacity to deliver filled antibiotics in a timeframe necessary to eradicate bacteria in biofilms. This work shows affinity polymers can fill high levels of antibiotics post-implantation independent of biofilm presence potentially enabling device rescue, rather than removal, in case of infection.