Non-antibacterial tetracycline formulations: Clinical applications in dentistry and medicine

Ying Gu, Clay Walker, Maria E. Ryan, Jeffrey B. Payne, Lorne M. Golub

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

In 1983, it was first reported that tetracyclines (TCs) can modulate the host response, including (but not limited to) inhibition of pathologic matrix metalloproteinase (MMP) activity, and by mechanisms unrelated to the antibacterial properties of these drugs. Soon thereafter, strategies were developed to generate nonantibacterial formulations (subantimicrobial-dose doxycycline; SDD) and compositions (chemically modified tetracyclines; CMTs) of TCs as host-modulating drugs to treat periodontal and other inflammatory diseases. This review focuses on the history and rationale for the development of: (a) SDD which led to two government-approved medications, one for periodontitis and the other for acne/rosacea and (b) CMTs, which led to the identification of the active site of the drugs responsible for MMP inhibition and to studies demonstrating evidence of efficacy of the most potent of these, CMT-3, as an anti-angiogenesis agent in patients with the cancer, Kaposi's sarcoma, and as a potential treatment for a fatal lung disease (acute respiratory distress syndrome; ARDS). In addition, this review discusses a number of clinical studies, some up to 2 years' duration, demonstrating evidence of safety and efficacy of SDD formulations in humans with oral inflammatory diseases (periodontitis, pemphigoid) as well as medical diseases, including rheumatoid arthritis, post-menopausal osteopenia, type II diabetes, cardiovascular diseases, and a rare and fatal lung disease, lymphangioleiomyomatosis.

Original languageEnglish (US)
Pages (from-to)1-14
Number of pages14
JournalJournal of Oral Microbiology
Volume4
Issue number2012
DOIs
StatePublished - 2012

Keywords

  • Clinical applications
  • Host-modulation
  • Matrix metalloproteinase inhibitors
  • Tetracyclines

ASJC Scopus subject areas

  • Dentistry (miscellaneous)
  • Microbiology (medical)
  • Infectious Diseases

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