Plant-Made Biopharmaceuticals Target Dental Plaque, Gum Tissues

PRNewswire: October 10, 2016 – PHILADELPHIA, PA, U.S.A. – Biopharmaceuticals like insulin have been used for decades in medical practice, but dental medicine has few such drugs and those that are used are delivered invasively, often through gum surgery.

Now, a report in Biomaterials by Penn Dental Medicine’s Dr. Michel Koo and Dr. Henry Daniell suggests a new approach for delivering a biopharmaceutical to treat and prevent oral diseases, including dental caries (cavities). Caries predominantly affect children and adults of lower socioeconomic status and account for over $40 billion in health-care spending annually.

Using plants to produce antimicrobial peptides, the researchers were able to kill tooth-decay-causing bacteria and thwart their ability to form biofilms on a tooth-like surface with a single topical treatment. The peptides were even more effective when combined with an enzyme that degrades the matrix that surrounds bacteria inside biofilms. They also demonstrated that these peptides could be taken up by gingival cells.

The platform is low-cost compared to the current means of producing biopharmaceuticals and presents a unique opportunity to develop an affordable therapeutic approach that simultaneously attacks disease-causing plaque and promotes gum health.

To address the prohibitive cost of antimicrobial peptide production, the researchers turned to Daniell’s plant-based drug production platform. It entails bombarding a plant leaf with a cloned gene of interest to reprogram the chloroplasts to synthesize the associated protein. In this case, they coaxed plants to produce two antimicrobial peptides, retrocyclin and protegrin. Both peptides have complex secondary structures, making them expensive to produce by traditional means. But the researchers found they could literally grow them in Daniell’s greenhouse and replicate their unique secondary structures in the plant’s leaves.

Koo’s lab tested whether the plant-made agents could prevent biofilm creation. They exposed a saliva-coated tooth-like surface to the plant-made protegrin for 30 minutes, then exposed the surface to S. mutans cells along with sugar, and found that it significantly impaired the ability of the bacterium to form a biofilm compared to an untreated surface.

To see whether the antimicrobials could also act therapeutically, they next exposed a pre-formed biofilm on the tooth-mimicking surface to either protegrin alone or a combination of protegrin and a matrix-degrading enzyme. The combination was powerful—able to degrade 60% of the matrix and killing even more bacteria than the antimicrobial alone.

Beyond topical-drug delivery, Daniell’s lab has been investigating molecular “tags” to route protein drugs to human cells to treat several diseases. In this context, delivering growth hormones or other such drugs to gum tissues for wound healing or bone regeneration is of paramount importance to enhance oral health. Their study found that the plant-made antimicrobial peptides could be taken up by human cells in the oral cavity.

“This opens up a completely new field for drug delivery with a topical agent,” Daniell said.

A collaboration with Johnson & Johnson Consumer Inc. will enable Koo and Daniell to continue optimizing their antimicrobialenzyme production system. One possibility, they note, is a chewing gum laced with antimicrobial peptides that could slowly release as one chews.