The use of protein drugs, which derive from biological sources, has been limited in the field of dental medicine due to high costs and invasive delivery methods. But a new report from the University of Pennsylvania School of Dental Medicine suggests a new approach for delivering a protein drug that can treat and prevent oral disease including dental caries, commonly known as cavities. The researchers were able to kill tooth-decay-causing bacteria and prevent them from forming biofilms on a tooth-like surface using a single topical treatment of antimicrobial peptides produced by plants. The study also showed that these peptides could impact periodontal and gingival cells, which means the new delivery method could help treat diseases that affect the gum tissues.
The novel platform is a relatively cost-effective method of producing biopharmaceuticals and could lead to the development of an affordable therapeutic approach to attack plaque and promote gum health.
“As scientists we have many opportunities to develop breakthrough treatments but cost is a huge obstacle,” said Hyun (Michel) Koo, co-corresponding author on the study and professor in the department of orthodontics and divisions of pediatric dentistry and community oral health in Penn Dental Medicine. “What makes this approach so exciting is not only the science but, because the production costs are low, the feasibility of getting the therapy to the population who truly needs yet can’t afford it.”
Dr. Koo partnered with co-corresponding author Henry Daniell, director of translational research and professor in Penn Dental Medicine’s department of biochemistry and pathology, who created groundbreaking plant-produced therapeutics for several important human infectious and inherited diseases.
“It was a synergism,” Dr. Daniell said. “Bringing our research together led to this new concept of a topical protein drug made in plants that can both kill bacteria and break down the oral biofilm.”
The researchers combined antimicrobial peptides with enzymes that can break down the biofilm matrix and used a plant-based drug production platform to reduce the cost. The process bombards a plant leaf with gold particles coated in a cloned gene in order to reprogram the chloroplasts to synthesize the associated protein. For the study, the researchers used the process to manipulate plants to produce two antimicrobial peptides, retrocyclin and protegrin.
To test whether the plant-made agents could prevent biofilm from forming, 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. They found that the protegrin significantly impaired the ability of the bacterium to form a biofilm compared to an untreated surface.
Next, they exposed a pre-formed biofilm on the tooth-mimicking surface to either protegrin alone or a combination of protegrin along with a matrix-degrading enzyme to test the therapeutic possibilities. While the enzyme alone had no effect and the antimicrobial alone had some effect, the combination was able to successfully degrade 60% of the matrix and kill even more bacteria.
“A single topical treatment was capable of disrupting the biofilm,” Dr. Koo said. “Its effectiveness was comparable to that of chlorhexidine, which is considered the ‘gold standard’ for oral antimicrobial therapy.”
The study also showed that the plant-made antimicrobial peptides could be taken up by human cells in the oral cavity.
A collaboration with Johnson & Johnson Consumer Inc. will allow the researchers to continue developing the antimicrobial-enzyme production system. They may create a chewing gum laced with antimicrobial peptides or investigate growing the peptides in the betel leaf, which is commonly chewed in some Asian cultures.