Controlling the release of peptide antimicrobial agents from surfaces

被引:210
|
作者
Shukla, Anita [1 ]
Fleming, Kathleen E. [1 ]
Chuang, Helen F. [1 ]
Chau, Tanguy M. [1 ]
Loose, Christopher R. [1 ]
Stephanopoulos, Gregory N. [1 ]
Hammond, Paula T. [1 ]
机构
[1] MIT, Dept Chem Engn, Cambridge, MA 02139 USA
基金
美国国家科学基金会;
关键词
Layer-by-layer assembly; Polyelectrolyte multilayer film; Antimicrobial peptides; Local drug delivery; POLYELECTROLYTE MULTILAYER FILMS; LAYER THIN-FILMS; EXPONENTIAL-GROWTH; INNATE IMMUNITY; POLYMER-FILMS; PLASMID DNA; BACTERIA; DELIVERY; ANTIBACTERIAL; INFECTIONS;
D O I
10.1016/j.biomaterials.2009.11.082
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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 mu g/cm(2). 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. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2348 / 2357
页数:10
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