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.

Review on the current status of polymer degradation: a microbial approach

“…Some microorganisms are reported to change their morphology (e.g., Bacillus subtilis, Caulobacter crescentus) under harsh conditions, which allows them to exist in a hostile environment (O'Toole et al 2000). In the initial stage, microorganisms produce some proteins such as collagen, fibrin, fibronectin and laminin as a coating material, which help in cell-to-cell adhesion in biofilm (Bryers et al 2006;Simoes et al 2010). Biofilms exist as a matrix of extracellular polymeric substance (EPS) that depends on the surrounding conditions; it consists of a series of biological and physical changes during matrix formation and from the three-dimensional structure (Prakash et al 2003;Bryers et al 2006;Simoes et al 2010).…”

“…In the initial stage, microorganisms produce some proteins such as collagen, fibrin, fibronectin and laminin as a coating material, which help in cell-to-cell adhesion in biofilm (Bryers et al 2006;Simoes et al 2010). Biofilms exist as a matrix of extracellular polymeric substance (EPS) that depends on the surrounding conditions; it consists of a series of biological and physical changes during matrix formation and from the three-dimensional structure (Prakash et al 2003;Bryers et al 2006;Simoes et al 2010). (Gu 2003) Microbial species grow on a wide variety of surfaces, i.e., inert or living.…”

Polyanhydrides

“…Furthermore, effect of media on degradation rate was studied and found to increase marginally better (14%) in media containing actively growing bacterial culture than sterile media. A signifi cant reduction in formation of Pseudomonas aeruginosa biofi lm in a longterm (3 day) study with the salicylic acid containing polymers was demonstrated and a pathway was postulated using P. aeruginosa pMHLAS, containing a fl uorescent reporter gene which involved inhibition of the las quorum sensing system [53] . In another study, a clear difference was seen between bacterial strains that form biofi lms at the air -liquid interface (top -forming) and those that form at the surface -liquid interface (bottom -forming).…”

In Vivo Performance of Melimine as an Antimicrobial Coating for Contact Lenses in Models of CLARE and CLPU

“…Alternative antimicrobial coatings such as salicylic acid, 11 quaternary ammonium compounds, 12 and chlorhexidine 13 have also been trialed. However, in many cases development of microbial resistance 14 makes these forms of therapy short-lived.…”