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.
Biomaterials and Tissue Engineering Group, Burdett Institute of Gastrointestinal Nursing, Kings College London, London, UK.
J J
JJ
Blaker
J
J
Pratten
D
D
Ready
J C
JC
Knowles
A
A
Forbes
R M
RM
Day
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