Assessment of antimicrobial microspheres as a prospective novel treatment targeted towards the repair of perianal fistulae

BACKGROUND: None of the proposed materials tested for the management of perianal fistulae has proven to be a definitive treatment. AIM: To assess a new repair scaffold and drug delivery device conceived to target perianal fistula repair. METHODS: Poly(D,L-lactide-co-glycolide) porous microspheres containing either antibacterial silver-releasing degradable phosphate glass or metronidazole were prepared using thermally induced phase separation. RESULTS: Ion- and drug-release profiling of the microspheres revealed continued release of silver ions from microspheres filled with silver-doped phosphate glass and high encapsulation efficiency for metronidazole [78% and 82% for microspheres loaded with 2.5% and 1.3% (w/w), respectively]. Microbicidal activity was confirmed by growth inhibition of bacterial species (Staphylococcus aureus, Escherichia coli and Bacteroides fragilis), which characteristically dominate the colonization of perianal fistula tracts. Microspheres containing >3 mol% silver or metronidazole resulted in strong bacterial inhibition/kill against B. fragilis; the presence of one sphere containing >3 mol% silver had a potent inhibitory effect against all the microbes studied. Microspheres became rapidly integrated with host tissue following subcutaneous implantation into a rodent wound model. CONCLUSION: The study demonstrates a novel scaffold for guided tissue regeneration providing local release of antimicrobial agents sufficient to counter bacterial colonization and warrants further investigation.