title: 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.
abstract: 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.
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA 98195, USA. jbryers@u.washington.edu
authors.forename: James D
authors.initials: JD
authors.lastname: Bryers
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Jarvis
authors.forename: Jason
authors.initials: J
authors.lastname: Lebo
authors.forename: Almudena
authors.initials: A
authors.lastname: Prudencio
authors.forename: Themis R
authors.initials: TR
authors.lastname: Kyriakides
authors.forename: Kathryn
authors.initials: K
authors.lastname: Uhrich
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000378:metabolism; D018441:Biofilms / Q000187:drug effects*; D005547:Foreign Bodies / Q000276:immunology*; D007107:Immune System / Q000187:drug effects*; D049388:Polyanhydrides / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D020156:Salicylic Acid / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001672:Biocompatible Materials; D049388:Polyanhydrides; D020156:Salicylic Acid