Browsing by Author "Norris, Patrick Michael"

Now showing 1 - 3 of 3

Ultrasonically controlled antibiotic release from hydrogel coatings for biofilm prevention
(Montana State University - Bozeman, College of Engineering, 2004) Norris, Patrick Michael; Chairperson, Graduate Committee: Aleksandra Vinogradov
Medical devices are routinely employed in healthcare settings since they provide clinicians with a means of administering nutrients, drawing blood samples and drug delivery. However, local and systemic infections are frequently associated with the use of medical devices and implants. In fact, implanted devices often provide a highly suitable surface for bacterial adhesion and colonization resulting in the formation of complex, differentiated and structured communities known as biofilms. Once a biofilm infection is established, conventional treatments frequently fail as bacteria in the form of biofilms are much more resistant to antibiotics than their planktonic counterparts. A variety of implantable drug-delivery systems have been developed to combat biofilm related infections. The main goal of this research was to investigate the effectiveness of a drugdelivery method using polymer hydrogels. The University of Washington Engineered Biomaterials (UWEB) group has developed a novel drug-delivery polymer matrix consisting of a poly 2-hydroxyethyl methacrylate hydrogel coated with ordered methylene chains forming an ultrasound-responsive coating. The polymer hydrogel was loaded with ciprofloxacin, an antibiotic well known for its action against gram-negative bacteria. This system was able to retain the drug inside the polymer in the absence of ultrasound but showed a significant drug release when low intensity ultrasound was applied. A consistent experimental program has been developed to determine the effectiveness of the UWEB hydrogels against Pseudomonas aeruginosa biofilms. Biofilms were grown on hydrogel surfaces in flowcells. Ultrasound was applied for twenty minutes every twenty four hours for three days using a 43 kHz ultrasonic bath. Confocal images were taken both before and after ultrasound application. The confocal data was then analyzed quantitatively using the biofilm analysis software package, COMSTAT. In addition, a numerical model was developed to demonstrate and characterize drug-delivery from hydrogel surfaces. Experimental results showed that biofilm accumulation on ciprofloxacin loaded hydrogels with ultrasound induced drug-delivery was significantly reduced compared to biofilms grown in control experiments. The results of these studies may ultimately facilitate future development of medical devices sensitive to external ultrasonic impulses, capable of treating or preventing biofilm growth via "on demand" drug release.
Ultrasonically controlled release of ciprofloxacin from self-assembled coatings on poly(2-hydroxyethyl methacrylate) hydrogels for Pseudomonas aeruginosa biofilm prevention
(2005-10) Norris, Patrick Michael; Noble, M.; Francolini, I.; Vinogradov, A. M.; Stewart, Philip S.; Ratner, B. D.; Costerton, J. William; Stoodley, Paul
Indwelling prostheses and subcutaneous delivery devices are now routinely and indispensably employed in medical practice. However, these same devices often provide a highly suitable surface for bacterial adhesion and colonization, resulting in the formation of complex, differentiated, and structured communities known as biofilms. The University of Washington Engineered Biomaterials group has developed a novel drug delivery polymer matrix consisting of a poly(2-hydroxyethyl methacrylate) hydrogel coated with ordered methylene chains that form an ultrasound-responsive coating. This system was able to retain the drug ciprofloxacin inside the polymer in the absence of ultrasound but showed significant drug release when low-intensity ultrasound was applied. To assess the potential of this controlled drug delivery system for the targeting of infectious biofilms, we monitored the accumulation of Pseudomonas aeruginosa biofilms grown on hydrogels with and without ciprofloxacin and with and without exposure to ultrasound (a 43-kHz ultrasonic bath for 20 min daily) in an in vitro flow cell study. Biofilm accumulation from confocal images was quantified and statistically compared by using COMSTAT biofilm analysis software. Biofilm accumulation on ciprofloxacin-loaded hydrogels with ultrasound-induced drug delivery was significantly reduced compared to the accumulation of biofilms grown in control experiments. The results of these studies may ultimately facilitate the future development of medical devices sensitive to external ultrasonic impulses and capable of treating or preventing biofilm growth via "on-demand" drug release.
Usnic acid, a natural antimicrobial agent able to inhibit bacterial biofilm formation on polymer surfaces
(2004-10) Francolini, I.; Norris, Patrick Michael; Donelli, G.; Stoodley, Paul
In modern medicine, artificial devices are used for repair or replacement of damaged parts of the body, delivery of drugs, and monitoring the status of critically ill patients. However, artificial surfaces are often susceptible to colonization by bacteria and fungi. Once microorganisms have adhered to the surface, they can form biofilms, resulting in highly resistant local or systemic infections. At this time, the evidence suggests that (+)-usnic acid, a secondary lichen metabolite, possesses antimicrobial activity against a number of planktonic gram-positive bacteria, including Staphylococcus aureus, Enterococcus faecalis, and Enterococcus faecium. Since lichens are surface-attached communities that produce antibiotics, including usnic acid, to protect themselves from colonization by other bacteria, we hypothesized that the mode of action of usnic acid may be utilized in the control of medical biofilms. We loaded (+)-usnic acid into modified polyurethane and quantitatively assessed the capacity of (+)-usnic acid to control biofilm formation by either S. aureus or Pseudomonas aeruginosa under laminar flow conditions by using image analysis. (+)-Usnic acid-loaded polymers did not inhibit the initial attachment of S. aureus cells, but killing the attached cells resulted in the inhibition of biofilm. Interestingly, although P. aeruginosa biofilms did form on the surface of (+)-usnic acid-loaded polymer, the morphology of the biofilm was altered, possibly indicating that (+)-usnic acid interfered with signaling pathways.