title: Plasma-modified nitric oxide-releasing polymer films exhibit time-delayed 8-log reduction in growth of bacteria.
abstract: Tygon(®) and other poly(vinyl chloride)-derived polymers are frequently used for tubing in blood transfusions, hemodialysis, and other extracorporeal circuit applications. These materials, however, tend to promote bacterial proliferation which contributes to the high risk of infection associated with device use. Antibacterial agents, such as nitric oxide donors, can be incorporated into these materials to eliminate bacteria before they can proliferate. The release of the antimicrobial agent from the device, however, is challenging to control and sustain on timescales relevant to blood transport procedures. Surface modification techniques can be employed to address challenges with controlled drug release. Here, surface modification using H2O (v) plasma is explored as a potential method to improve the biocompatibility of biomedical polymers, namely, to tune the nitric oxide-releasing capabilities from Tygon films. Film properties are evaluated pre- and post-treatment by contact angle goniometry, x-ray photoelectron spectroscopy, and optical profilometry. H2O (v) plasma treatment significantly enhances the wettability of the nitric-oxide releasing films, doubles film oxygen content, and maintains surface roughness. Using the kill rate method, the authors determine both treated and untreated films cause an 8 log reduction in the population of both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Notably, however, H2O (v) plasma treatment delays the kill rate of treated films by 24 h, yet antibacterial efficacy is not diminished. Results of nitric oxide release, measured via chemiluminescent detection, are also reported and correlated to the observed kill rate behavior. Overall, the observed delay in biocidal agent release caused by our treatment indicates that plasma surface modification is an important route toward achieving controlled drug release from polymeric biomedical devices.
authors.affiliation: Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523-1872.
authors.forename: Michelle N
authors.initials: MN
authors.lastname: Mann
authors.affiliation: Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523-1872.
authors.forename: Bella H
authors.initials: BH
authors.lastname: Neufeld
authors.affiliation: Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523-1872.
authors.forename: Morgan J
authors.initials: MJ
authors.lastname: Hawker
authors.affiliation: Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523-1872.
authors.forename: Adoracion
authors.initials: A
authors.lastname: Pegalajar-Jurado
authors.affiliation: Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523-1872.
authors.forename: Lindsey N
authors.initials: LN
authors.lastname: Paricio
authors.affiliation: Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523-1872; School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado 80523-1872; and Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, Colorado 80523-1872.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Reynolds
authors.affiliation: Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523-1872.
authors.forename: Ellen R
authors.initials: ER
authors.lastname: Fisher
mesh_terms: D000890:Anti-Infective Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D004926:Escherichia coli / Q000187:drug effects* / Q000502:physiology; D050296:Microbial Viability / Q000187:drug effects; D009569:Nitric Oxide / Q000493:pharmacokinetics* / Q000494:pharmacology*; D010949:Plasma / Q000382:microbiology; D011108:Polymers / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology; D013499:Surface Properties
chemical_list: D000890:Anti-Infective Agents; D020099:Coated Materials, Biocompatible; D011108:Polymers; D009569:Nitric Oxide