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.


OBJECTIVE
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.


CONCLUSIONS
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.
Blaker
J J
JJ
Biomaterials and Tissue Engineering Group, Burdett Institute of Gastrointestinal Nursing, Kings College London, London, UK.
Pratten
J
J
Ready
D
D
Knowles
J C
JC
Forbes
A
A
Day
R M
RM
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D001672:Biocompatible Materials / Q000627:therapeutic use; D016503:Drug Delivery Systems; D006801:Humans; D008795:Metronidazole / Q000008:administration & dosage*; D008863:Microspheres; D010481:Perianal Glands / Q000502:physiology; D011100:Polyglycolic Acid; D011446:Prospective Studies; D012003:Rectal Fistula / Q000188:drug therapy* / Q000601:surgery; D012834:Silver / Q000008:administration & dosage*; D054457:Tissue Scaffolds; D014945:Wound Healing / Q000187:drug effects*
D000890:Anti-Infective Agents; D001672:Biocompatible Materials; D008795:Metronidazole; D011100:Polyglycolic Acid; D012834:Silver