In a new study, a “bioadhesive” coating developed at Brown University significantly improved the intestinal absorption into the bloodstream of nanoparticles that someday could carry protein drugs such as insulin.
Such a step is necessary for drugs taken by mouth, rather than injected directly into the blood.
For protein-based drugs such as insulin to be taken orally rather than injected, bioengineers need to find a way to shuttle them safely through the stomach to the small intestine where they can be absorbed and distributed by the bloodstream. Progress has been slow, but in a new study, researchers report an important technological advance: They show that a “bioadhesive” coating significantly increased the intestinal uptake of polymer nanoparticles in rats and that the nanoparticles were delivered to tissues around the body in a way that could potentially be controlled.
“The results of these studies provide strong support for the use of bioadhesive polymers to enhance nano- and microparticle uptake from the small intestine for oral drug delivery,” wrote the researchers in the Journal of Controlled Release, led by corresponding author Edith Mathiowitz, professor of medical science at Brown University.
Mathiowitz, who teaches in Brown’s Department of Molecular Pharmacology, Physiology, and Biotechnology, has been working for more than a decade to develop bioadhesive coatings that can get nanoparticles to stick to the mucosal lining of the intestine so that they will be taken up into its epithelial cells and transferred into the bloodstream. The idea is that protein-based medicines would be carried in the nanoparticles.
In the new study, which appeared online June 21, Mathiowitz put one of her most promising coatings, a chemical called PBMAD, to the test both on the lab bench and in animal models. Mathiowitz and her colleagues have applied for a patent related to the work, which would be assigned to Brown University.
In prior experiments, Mathiowitz and her group have shown not only that PBMAD has bioadhesive properties, but also that it withstands the acidic environment of the stomach and then dissolves in the higher pH of the small intestine.
Adhere, absorb, arrive
The newly published results focused on the question of how many particles, whether coated with PBMAD or not, would be taken up by the intestine and distributed to tissues. For easier tracking throughout the body, Mathiowitz’s team purposely used experimental and control particles made of materials that the body would not break down. Because they were “non-erodible” the particles did not carry any medicine.
The researchers used particles about 500 nanometers in diameter made of two different materials: polystyrene, which adheres pretty well to the intestine’s mucosal lining, and another plastic called PMMA, that does not. They coated some of the PMMA particles in PBMAD, to see if the bioadhesive coating could get PMMA particles to stick more reliably to the intestine and then get absorbed.
via Brown University
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