Clinical assessment of the effect of a matrix metalloproteinase inhibitor on aphthous ulcers

Acta Odontol Scand. 2009;67(1):25-9. doi: 10.1080/00016350802526559.


Objective: Aphthous ulceration is a common form of recurrent ulceration of the oral mucosa. Numerous treatments have been tried as a means of relieving pain, disinfecting the ulcer base, and reducing inflammation, but with limited success. Tetracycline and its derivatives have been shown to be inhibitors of matrix metalloproteinases (MMPs), which are part of the inflammatory response and contribute to the breakdown of tissue in the ulcer. Of the commercially available tetracyclines, doxycycline has shown the best inhibition of the MMPs. The aim of this study was to test clinically whether the inhibitory effect of a low-dose doxycycline in a hydrogel on MMPs would speed the recovery of oral ulceration.

Material and methods: Forty-nine patients participated in a randomized, double-blind, placebo-controlled trial.

Results: Sixty-eight percent of ulcers had healed by the third day of treatment with the doxycycline gel, whereas only 25% of the patients receiving the placebo reported healing of their ulcers within 3 days. Patients treated with the docycline gel recounted faster reduction in pain during the treatment period than the placebo group did.

Conclusions: Incorporation of low-dose doxycycline in a muco-adhesive gel has been demonstrated to have potential in the treatment of recurrent oral ulceration. It is concluded that MMP enzymes can be inhibited by low doses of doxycycline below levels likely to disrupt the oral flora.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Adolescent
  • Adult
  • Aged
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Doxycycline / therapeutic use*
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Gels
  • Humans
  • Male
  • Matrix Metalloproteinase Inhibitors*
  • Middle Aged
  • Pain Measurement
  • Stomatitis, Aphthous / drug therapy*
  • Stomatitis, Aphthous / enzymology
  • Treatment Outcome
  • Young Adult


  • Enzyme Inhibitors
  • Gels
  • Matrix Metalloproteinase Inhibitors
  • Doxycycline