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Antimicrobial Agents and Chemotherapy, October 2005, p. 4272-4279, Vol. 49, No. 10
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.10.4272-4279.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Ultrasonically Controlled Release of Ciprofloxacin from Self-Assembled Coatings on Poly(2-Hydroxyethyl Methacrylate) Hydrogels for Pseudomonas aeruginosa Biofilm Prevention

P. Norris,1,2 M. Noble,3 I. Francolini,1,4 A. M. Vinogradov,2 P. S. Stewart,1 B. D. Ratner,3 J. W. Costerton,1,5 and P. Stoodley1,2,6*

Center for Biofilm Engineering, 366 EPS Building, Montana State University—Bozeman, Bozeman, Montana 59717,1 Department of Mechanical Engineering, Montana State University—Bozeman, Bozeman, Montana 59717,2 University of Washington Engineered Biomaterials, Department of Bioengineering, University of Washington, Seattle, Washington 98195-1720,3 University of Rome "La Sapienza," Department of Chemistry, Piazzale Aldo Moro, 5-00185, Rome, Italy,4 University of Southern California, Center for Biofilms, Division 5-CHC, Los Angeles, California 90033,5 Center for Genomic Sciences, Allegheny Singer Research Institute, 320 East North Ave., Pittsburgh, Pennsylvania 152126

Received 1 April 2005/ Returned for modification 15 June 2005/ Accepted 11 July 2005

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.

* Corresponding author. Mailing address: Center for Genomic Sciences, Allegheny-Singer Research Institute, 320 East North Ave., Pittsburgh, PA 15212. Phone: (412) 359-6876. Fax: (412) 359-6995. E-mail: pstoodle{at}wpahs.org.

Antimicrobial Agents and Chemotherapy, October 2005, p. 4272-4279, Vol. 49, No. 10
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.10.4272-4279.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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