David Plackett, Jason Asnis, John Jackson, and Helen Burt
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia
Catheter-associated urinary tract infections (CAUTIs) are amongst the most common nosocomial infections in modern hospitals [1]. According to some estimates, 50% of patients with short-term catheters and a much higher percentage of patients with longterm in-dwelling catheters develop such infections. Although silicone catheters coated or infused with silver or nitrofurazone, a topical anti-infective, have been available, these catheters are reported to suffer from short drug elution times and lack of antibiotic efficacy [2]. In order to address the needs in this area, we launched a NanoBridgeassociated research project based on potential use of nanocrystalline cellulose (CNC) and three concepts: 1) polydopamine (PDA) priming of silicone to provide durable, biocompatible and reactive surfaces for further coating, 2) synergistic combinations of silver and gentamicin, an aminoglycoside antibiotic, as a coating system over a PDA primer, and 3) the evaluation of PDA-bound CNC/silver/gentamicin combinations as catheter coating systems and as a route to extended drug release profiles. The use of PDA as a coating for virtually any kind of organic or inorganic surface, with potentially diverse applications, has attracted continuing interest based largely on the seminal work of the Messersmith group at Northwestern University [3]. The application of silver to enhance antibiotic activity has also gained increasing attention as a route to more effective antimicrobial therapies [4]. In our project, the research objectives were to characterize the binding and release of silver and gentamicin from CNC and the binding and release of both drugs in combination with CNC from PDA-primed surfaces. The presentation will review the key findings from this project and outline the next steps required to confirm the value of this CNC application in the medical field.
References
1. Trautner, B.W. (2010) Curr. Opin. Infect. Dis. 23(1), 76-82.
2. Johnson, J.R., Kuskowski, M.A., Wilt, T.J. (2006) Annal. Int. Med. 144(2), 116- 126.
3. Lee, H., Dellatore, S.M., Miller, W.M., Messersmith, P.B. (2007) Science, 318, 426-430.
4. Morones-Ramirez, J.R., Winkler, J.A., Spina, C.S., Collins, J.J. (2013) Sci. Transl. Med. 5, 190ra81.