Biodegradation of poly(anhydride-esters) into non-steroidal anti-inflammatory drugs and their effect on Pseudomonas aeruginosa biofilms in vitro and on the foreign-body response in vivo

Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
Biomaterials (Impact Factor: 8.56). 11/2006; 27(29):5039-48. DOI: 10.1016/j.biomaterials.2006.05.034
Source: PubMed


The ability of poly(anhydride-esters) composed of non-steroidal anti-inflammatory drugs that biodegrade to salicylic acid (SA) and adipic acid to prevent colonization by Pseudomonas aeruginosa and their effects on the foreign-body response were studied in vitro and in vivo, respectively. Soluble SA in bacterial medium at concentrations up to 300 mg/L did not affect the growth rate or viability of P. aeruginosa, indicating that SA does not exhibit a direct toxicity effect on the bacterium. Batch degradation rates of the salicylate-based polymer in the presence of an actively growing bacterial culture only marginally (14%) increased relative to polymer degradation rates in sterile medium. Short-term (3h) bacterial adhesion studies in agitated batch systems indicated a 47% reduction in the rate of P. aeruginosa adhesion relative to a control polymer that does not release SA upon biodegradation. Long-term (3-day) biofilm accumulation studies indicated a dramatic reduction in biofilm formation on salicylate-based polymer versus controls. A recombinant P. aeruginosa pMHLAS, containing a fluorescent reporter gene prior to the las regulon, was employed to determine whether salicylate-based polymer prevents biofilm formation by the released SA inhibiting quorum sensing pathways. Long-term biofilm accumulation studies with P. aeruginosa pMHLAS insinuate that salicylate-based polymer prevents biofilm accumulation by inhibiting the las quorum sensing system. Furthermore, unlike control polymer, salicylate-based polymer implanted subcutaneously for a period of 4 weeks-resisted cell-mediated degradation and remained intact. Histological and immunohistochemical analysis indicated a reduction in overall encapsulation and paucity of macrophages in the area of the salicylate-based polymer implant.

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Available from: James D Bryers, Sep 30, 2015
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    • "e l s e v i e r . c o m / l o c a t e / s a j b Staphylococcus epidermidis and Pseudomonas aeruginosa (Bryers et al., 2006; Farber et al., 1995). However, their use for cleaning of lenses and their storage containers remains limited and removal of the biofilm from contact lenses relies mainly on how often the disinfectant is replaced (Kilvington and Lonnen, 2009). "
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    South African Journal of Botany 04/2015; 99:115-121. DOI:10.1016/j.sajb.2015.03.192 · 0.98 Impact Factor
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    Biomaterials 12/2012; 33(35):8928–8933. DOI:10.1016/j.biomaterials.2012.09.011 · 8.56 Impact Factor
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    • "Acetylsalicylic acid has been shown to have activity against the yeast Candida albicans [22] [23], a common CAUTI isolate. The possibility of controlled release of salicylic acid from materials to inhibit biofilms has been considered previously: SA-releasing poly(anhydride-ester) polymers have been shown to be potent inhibitors of P. aeruginosa biofilms [24]. Because these polymers release SA by hydrolysis of the main chain bonds of the polymer, materials made from these polymers lose mechanical strength and structural integrity as they degrade, a property suitable for some applications but not others. "
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