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.
In the new study, 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.
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.
First the team, including authors Joshua Reineke of Wayne State University and Daniel Cho of Brown, performed basic benchtop tests to see how well each kind of particles adhered. The PBMAD-coated particles proved to have the strongest stickiness to intestinal tissue, binding more than twice as strongly as the uncoated PMMA particles and about 1.5 times as strongly as the polystyrene particles.
The main experiment, however, involved injecting doses of the different particles into the intestines of rats to see whether they would be absorbed and where those that were taken up could be found five hours later. Some rats got a dose of the polystyrene particles, some got the uncoated PMMA and some got the PBMAD-coated PMMA particles.
Measurements showed that the rats absorbed 66.9 percent of the PBMAD-coated particles, 45.8 percent of the polystyrene particles and only 1.9 percent of the uncoated PMMA partcles.
Meanwhile, the different particles had very different distribution profiles around the body. More than 80 percent of the polystyrene particles that were absorbed went to the liver and another 10 percent went to the kidneys. The PMMA particles, coated or not, found their way to a much wider variety of tissues, although in different distributions. For example, the PBMAD-coated particles were much more likely to reach the heart, while the uncoated ones were much more likely to reach the brain.
The apparent fact that the differing surface properties of the similarly sized particles had such distinct distributions in the rats’ tissues after the same five-hour period suggests that scientists could learn to tune particles to reach specific parts of the body, essentially targeting doses of medicines taken orally, Mathiowitz said.
For now, she and her group have been working hard to determine the biophysics of how the PBMAD-coated particles are taken up by the intestines. More work also needs to be done, for instance to demonstrate actual delivery of protein-based medicines in sufficient quantity to tissues where they are needed.
This story is reprinted from material from Brown University, with editorial changes made by Materials Today. The views expressed in this article do not necessarily represent those of Elsevier. Link to original source.