Peptide-mediated Attachment of Drug-loaded Microparticles to Medical Devices

DESCRIPTION (provided by applicant): Mediastinitis is a common and sometimes devastating complication following open heart surgery. Despite the use of prophylactic systemic antibiotics and improved surgical techniques, bacterial infection remains a serious complication following almost all surgical procedures including median sternotomy. When surgical site infections occur, they can be devastating with immense financial and psychological costs especially in at-risk patients such as diabetics, smokers, the elderly, and immunocompromised. New technologies that prevent microbial colonization of the at-risk tissues in a surgical site could clearly benefit society by decreasing infection rates. The need for further innovation in the local delivery of antibiotics is our motivation to develop a peptide-mediated system to attach drug-loaded microparticles to medical devices. Affinergy is developing bifunctional affinity peptides, called interfacial biomaterials (IFBMs), that promote the attachment and retention of drugs, proteins, and cells on the surface of medical devices. Using phage display, we have identified specific peptide sequences that bind with high affinity to a number of materials and biologics. Synthesizing a pair of these peptides as a single IFBM promotes the attachment of drug, protein, or cell directly to the surface of a medical device. While we have observed promising preliminary data with this technique using antibiotics, peptide-mediated coating of medical devices with drug loaded microparticles may hold additional advantages. There are likely additional drugs and additional medical devices we might target with this novel microparticle-coating strategy. Because there exist such a wide range of potential peptide-microparticle device combinations, in this proposal we will focus on the development of a microparticle coating for sternal wires to prevent mediastinitis. Therefore, the goal of this Phase I research plan is to first optimize drug loaded poly (lactic-co-glycolic acid) (PLGA) microparticle preparations at Affinergy. We will then characterize and optimize candidate PLGA: metal IFBMs. Finally, we will examine the antimicrobial efficacy and biocompatibility of IFBM targeted microparticles, determining if the microparticles increase the potential of Affinergy device coating technology. The aims presented here represent a proof-of-principle research program, which would be expanded to include new antibiotics and commercialization strategies during a subsequent Phase II funding period. In the future, microparticles: medical device IFBMs could be used to attach microparticles loaded with a wide variety of therapeutic molecules from antibiotics to prevent post-operative infection to local anesthetics to treat post- operative pain. PUBLIC HEALTH RELEVANCE: Post-operative infection is a common and sometimes devastating complication following open heart surgery. Despite the use of prophylactic systemic antibiotics and improved surgical techniques, infection remains a serious complication. The need for further innovation in localized antibiotic delivery is our motivation to develop a peptide-mediated attachment system for drug-loaded microparticles onto medical devices. Affinergy is developing bifunctional affinity peptides, called interfacial biomaterials (IFBMs), that promote the attachment and retention of drugs, proteins, and cells on the surface of medical devices. While we have observed promising preliminary data with this technique using antibiotics, peptide-mediated coating of medical devices with drug loaded microparticles may hold additional advantages. There are likely additional drugs and additional medical devices we might target with this novel microparticle coating strategy. In this proposal we focus on the development of a microparticle coating for sternal wires to deliver antibiotics locally following open heart surgery. In the future, microparticle: medical device IFBMs could be used to attach microparticles loaded with a wide variety of therapeutic molecules from antibiotics to prevent post-operative infection to local anesthetics to treat post-operative pain.