Developing medications for children can be challenging. Taste and texture are important but safety is also a major concern.
At South Dakota State University, co-founder and Chief Scientific Officer of Tranzderm Solutions, Om Perumal, is addressing this by adapting a corn protein-based drug delivery method to oral paediatric formulations.
He explained, simply:
Our idea is to use products kids like.
The drug delivery system uses zein, a protein found in dried distillers grain, a co-product of ethanol production, to encapsulate the medication. The nanoparticles are approximately 500 times smaller than the diameter of a human hair.
To apply to oral paediatric formulations, Perumal'a team “modified the nanoparticles by coating them with milk proteins.”
Providing federal incentive
Before 1998, about 70% of the drugs used for children had not undergone clinical testing for the newborn to 17-year-old population.
“Drugs behave differently in children than adults,” Perumal explained.
However, the pharmaceutical industry did not have much incentive to test, because the paediatric medications make up only 10% of the pharmaceutical market.
To encourage the development of drugs customised for children, the US federal government passed the Best Pharmaceutical for Children’s Act in 2002. It grants incentives to drug companies conducting FDA-requested paediatric studies.
Adapting to paediatric market
The team's initial work targets infants and toddlers, who need either an oral suspension or a chewable form.
“Dissolving a drug that is not water soluble can result in a thick, uninviting suspension,” Perumal said.
“Using an excipient with high amounts of alcohol to dissolve the drug is out of the question for young children.”
We are developing formulas customised for children that are safe and can be flexible based on the age of the patient.
The zein nanoparticles, which are not water soluble, protect the drug and the milk protein coating makes them more water dispersible.
“We have the best of both worlds,” Perumal said.
In addition, the milk powder masks the drug’s taste.
“We can put the nanoparticles into a liquid, a chewable tablet or a capsule. We could even use them as food sprinkles.”
Identifying potential medications
The patent-pending drug delivery method can be optimised using different milk proteins, such as casein, lactoferrin and lactoglobulin. To mimic how the delivery system works, Perumal is testing the formulations using simulated gastric and intestinal fluid.
“We don’t want it to release in the food matrix,” he explained. The medication should be absorbed, typically within 24 hours, in the intestinal tract.
Thus far, milk has worked best, though experiments are underway to test the formulation in yogurt and other food matrices.
We could even use the nanoparticles as food sprinkles.
Perumal's first target medications are antiretrovirals, which HIV-positive children must take for a lifetime. Using a rat model, Perumal and his team found that his formulation has 2–4 times higher absorption than what is currently on the market.
Another target medication is a drug under investigation to treat neuroblastoma, a cancer which affects infants and children up to 10 years old.
Though neuroblastoma accounts for 6% of cancers in children, Perumal said no paediatric drug formulation is available for the investigational compound.
Furthermore, what works for children will be useful for patients who have swallowing difficulties, such as the elderly.
