title: Design of multi-drug release coatings targeting infection and inflammation.
abstract: Although infection and inflammation commonly coexist, there is a paucity of appropriate methods for concurrent localized delivery of antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) at appropriate concentrations and timescales. The commonly used therapeutic approach of systemic delivery of antibiotics and NSAIDs is associated with many complications, including rises in antibiotic resistant bacteria and severe gastrointestinal problems. As a potential solution, in this work we have assembled polymer multilayers to concurrently release therapeutic concentrations of an antibiotic, vancomycin, and an NSAID, diclofenac. Prior to film assembly, interactions between film components were thoroughly examined. Taking advantage of novel interactions found to exist between film components, several optimal film architectures were engineered using both dip and spray layer-by-layer assembly. A wide range of drug release profiles were obtained, with vancomycin delivery lasting from 4 hours to 2.3 days at final loadings of 13 to 30 μg/cm(2), while diclofenac released over 1.7 to 14 days at final loadings of 10 to 36 μg/cm(2). These drug release profiles have the potential to address a range of infection and inflammation requirements, from short term infection and inflammation eradication for trauma relief to infection prevention and long term inflammation mitigation from biomedical implants. Film-released vancomycin and diclofenac were found to be highly active against their respective targets in vitro, Staphylococcus aureus and cyclooxygenase. These films were also successfully applied to several medically relevant substrates, including intraocular lenses, bandages, and sutures, demonstrating potential for use as medical device coatings.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
authors.forename: Anita
authors.initials: A
authors.lastname: Shukla
authors.forename: Renée C
authors.initials: RC
authors.lastname: Fuller
authors.forename: Paula T
authors.initials: PT
authors.lastname: Hammond
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D004008:Diclofenac / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D004338:Drug Combinations; D004339:Drug Compounding; D015195:Drug Design; D004347:Drug Interactions; D007910:Lenses, Intraocular; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry; D012995:Solubility; D012996:Solutions; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D013499:Surface Properties; D014640:Vancomycin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D004338:Drug Combinations; D054852:Small Molecule Libraries; D012996:Solutions; D004008:Diclofenac; D014640:Vancomycin; D011451:Prostaglandin-Endoperoxide Synthases