Wang co-investigating high oral exposure to buprenorphine on dental caries

Professor Bing-Yan Wang, DDS, DMSc, PhD, of UTHealth Houston School of Dentistry is serving as the multiple principal investigator on a $700,000 yearly federal grant (R01 DE033321) from the National Institute of Dental and Craniofacial Research of the National Institutes of Health to study the impact of high oral exposure to buprenorphine on dental caries.

Wang is collaborating with Ming Hu, PhD, primary principle investigator and Diana S-L. Chow Endowed Professor of Drug Discovery and Development at the University of Houston, for the R01 project, titled “Elucidating High Oral Fluid Exposure Mechanisms of Buprenorphine to Reduce Dental Caries.”

Oral buprenorphine is the newest prescribed treatment for opioid use disorders (OUD). However, in January 2022, the Food and Drug Administration issued a warning for patients and prescribers stating the use of oral buprenorphine formulations, such as sublingual tablets and films, may cause serious dental problems, with some reported cases even in patients with no history of dental issues.

“Oral buprenorphine was marked by the FDA as causing dental caries, but the mechanism for this side effect is unknown,” Wang said. “My proposed studies will determine if oral buprenorphine causes dental caries through enhancing Streptococcus mutans’ virulence. I have been studying host influences on the virulence of S. mutans, a primary cariogenic bacterium, and this R01 grant provides means for me to further my studies in a new front.”

Wang and Hu hypothesize that mechanisms responsible for high oral fluid exposure to buprenorphine can be “elucidated and oral fluid exposure to buprenorphine exposure can be significantly reduced by saliva stimulant without reducing their systemic exposure.”

Wang’s research will include in vitro, ex vivo, and in vivo studies. A preclinical model of dental caries responsive to varying concentrations of buprenorphine will be established and used to evaluate the impact of high oral fluid exposure to buprenorphine on dental caries.

“My proposed studies will determine how increases in oral fluid exposure to buprenorphine affect cariogenesis of S. mutans using ex vivo and in vivo models of caries,” Wang said. “The comC gene — an essential gene for modulating many virulence properties — activation status in S. mutans and caries formation on the tooth will be assessed to determine if buprenorphine enhances S. mutans virulence and increases its cariogenesis in preclinical models.”

Wang will also determine if organic cation transporter models, more commonly referred to as Oct3, will have fewer caries when treated with oral buprenorphine, and if saliva stimulants that reduce oral fluid exposure to buprenorphine is effective in reducing caries.

The study aims to develop pharmacologic approaches to reduce oral cavity concentrations of buprenorphine without negatively impacting the drug’s systemic exposure and its intended use for medication assisted in OUD treatment.