Ultrasonically controlled antibiotic release from hydrogel coatings for biofilm prevention

Abstract

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.