title: Dual functional polyelectrolyte multilayer coatings for implants: permanent microbicidal base with controlled release of therapeutic agents.
abstract: Here we present a new bifunctional layer-by-layer (LbL) construct made by combining a permanent microbicidal polyelectrolyte multilayered (PEM) base film with a hydrolytically degradable PEM top film that offers controlled and localized delivery of therapeutics. Two degradable film architectures are presented: (1) bolus release of an antibiotic (gentamicin) to eradicate initial infection at the implant site, or (2) sustained delivery of an anti-inflammatory drug (diclofenac) to cope with inflammation at the site of implantation due to tissue injury. Each degradable film was built on top of a permanent base film that imparts the implantable device surface with microbicidal functionality that prevents the formation of biofilms. Controlled-delivery of gentamicin was demonstrated over hours and that of diclofenac over days. Both drugs retained their efficacy upon release. The permanent microbicidal base film was biocompatible with A549 epithelial cancer cells and MC3T3-E1 osteoprogenitor cells, while also preventing bacteria attachment from turbid media for the entire duration of the two weeks studied. The microbicidal base film retains its functionality after the biodegradable films have completely degraded. The versatility of these PEM films and their ability to prevent biofilm formation make them attractive as coatings for implantable devices.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
authors.forename: Sze Yinn
authors.initials: SY
authors.lastname: Wong
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Moskowitz
authors.forename: Jovana
authors.initials: J
authors.lastname: Veselinovic
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Rosario
authors.forename: Ksenia
authors.initials: K
authors.lastname: Timachova
authors.forename: Michael R
authors.initials: MR
authors.lastname: Blaisse
authors.forename: Renée C
authors.initials: RC
authors.lastname: Fuller
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Klibanov
authors.forename: Paula T
authors.initials: PT
authors.lastname: Hammond
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004008:Diclofenac / Q000494:pharmacology*; D004343:Drug Implants; D005839:Gentamicins / Q000494:pharmacology*; D006801:Humans; D008954:Models, Biological; D015394:Molecular Structure; D011108:Polymers / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D000890:Anti-Infective Agents; D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D004343:Drug Implants; D005839:Gentamicins; D011108:Polymers; C507253:poly(beta-amino ester); D004008:Diclofenac