Many drugs that children need are not available in liquid form, which makes them difficult or unsafe to administer orally to infants and young children, according to the U.S. National Institutes of Health. To address this problem in pediatric medicine, a team of Penn State food scientists has undertaken a research project to explore whether cow's milk protein - casein - can help deliver drugs that don't dissolve well in liquid medicines, funded by a two-year, $428,200 grant from the National Institutes of Health's (NIH) Eunice Kennedy Shriver National Institute of Child Health and Human Development.
A survey of pediatricians found 35 such drugs that urgently need child-friendly oral liquid formulations, noted research team leader Federico Harte, professor of food science and research team leader. His lab in Penn State's College of Agricultural Sciences has been experimenting with novel uses for casein for more than a decade.
"Want to use casein - the main protein in milk - to help deliver poorly soluble drugs as liquid medicines that do not contain ethanol, making them safer and easier to use for infants and children," he said. "Many drugs don't dissolve well in water, so they're often formulated using alcohol or other solvents. This project aims to replace those with casein-based amorphous solid dispersions - materials in which a drug is evenly distributed at the molecular level in a carrier that dissolves easily in water. If we are successful, this approach could lead to safer, ethanol-free liquid drug formulations using a natural, food-grade protein."
The researchers are working to create and optimize casein-based dispersions, as well as studying environmental conditions such as temperature, pH and processing conditions that allow casein to trap large amounts of drug - known as "high loading capacity," form stable dispersions and disperse instantly in water. They will test the dispersions using three hydrophobic - water-repelling - compounds: the antiviral drug Ritonavir, the diuretic drug Furosemide and a model natural fat compound called Tristearin. These compounds will act as test probes to see how well the system works with different insoluble substances.
The team will examine how stable the amorphous solid dispersions containing caseins are under different pH conditions and how the drug is released during simulated digestion. The researchers will assess what environmental triggers cause the drugs to leave the casein matrix and enter the surrounding water phase, where it can be absorbed. This analysis will help predict how the formulations behaves in the gastrointestinal tract, Harte explained.
The final phase of the study will involve testing the dispersions' bioavailability in animals
The researchers will compare the performance of two optimized casein-based formulations to ethanol-containing commercial formulations in mice. This step will show whether the drugs are absorbed into the bloodstream and whether the casein-based system works as well as or better than existing products, Harte said.
"This project aims to investigate whether casein can safely and effectively carry poorly soluble drugs and if these drugs can be formulated as water-based, ethanol-free liquids ideal for children that can be released and absorbed properly in the body," he said. "If successful, this approach could improve pediatric drug formulations and reduce reliance on alcohol-containing medicines."
Joshua Lambert, professor of food science, and Misha Kwasniewski, associate research professor of food science, are co-principal investigators on the research project. Andrea Soler and Caini Chen, doctoral students in food science, are working on the project.
