title: Controlling the release of peptide antimicrobial agents from surfaces.
abstract: Medical conditions are often exacerbated by the onset of infection caused by hospital dwelling bacteria such as Staphylococcus aureus. Antibiotics taken orally or intravenously can require large and frequent doses, further contributing to the sharp rise in resistant bacteria observed over the past several decades. These existing antibiotics are also often ineffective in preventing biofilm formation, a common cause of medical device failure. Local delivery of new therapeutic agents that do not allow bacterial resistance to occur, such as antimicrobial peptides, could alleviate many of the problems associated with current antibacterial treatments. By taking advantage of the versatility of layer-by-layer assembly of polymer thin films, ponericin G1, an antimicrobial peptide known to be highly active against S. aureus, was incorporated into a hydrolytically degradable polyelectrolyte multilayer film. Several film architectures were examined to obtain various drug loadings that ranged from 20 to 150 microg/cm2. Release was observed over approximately ten days, with varying release profiles, including burst as well as linear release. Results indicated that film-released peptide did not suffer any loss in activity against S. aureus and was able to inhibit bacteria attachment, a necessary step in preventing biofilm formation. Additionally, all films were found to be biocompatible with the relevant wound healing cells, NIH 3T3 fibroblasts and human umbilical vein endothelial cells. These films provide the level of control over drug loading and release kinetics required in medically relevant applications including coatings for implant materials and bandages, while eliminating susceptibility to bacterial resistance.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
authors.forename: Anita
authors.initials: A
authors.lastname: Shukla
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Fleming
authors.forename: Helen F
authors.initials: HF
authors.lastname: Chuang
authors.forename: Tanguy M
authors.initials: TM
authors.lastname: Chau
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Loose
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Stephanopoulos
authors.forename: Paula T
authors.initials: PT
authors.lastname: Hammond
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D018441:Biofilms; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D008422:Materials Testing; D051379:Mice; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D013211:Staphylococcus aureus / Q000187:drug effects; D013499:Surface Properties
chemical_list: D023181:Antimicrobial Cationic Peptides; D001672:Biocompatible Materials; D004337:Drug Carriers; C548664:ponericin G1, Pachycondyla goeldii