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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

Paper ID Volume ID Publish Year Pages File Format Full-Text
11820 760 2006 10 PDF Available
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 (3 h) 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.

Keywords
Biodegradable poly(anhydride-esters); Anti-biofilm control; Pseudomonas aeruginosa; Foreign-body response
First Page Preview
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
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 27, Issue 29, October 2006, Pages 5039–5048
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering