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Bioadhesive Coating for Protein-Based Drugs May Put an End to Insulin Injections

June 28th, 2013 Medgadget Editors News

protein-drug-coating

Scanning electron microscopy of PS (A), PMMA (B), and PBMAD/PMMA (C) nanospheres. Scale bars = 2.0 μm. Size distribution profiles for each formulation as measured by laser diffraction are also shown (D). Optical microscopy of PMMA (E, e) and PBMAD/PMMA (F, f) Large sphere approximately 5 μm 40x (upper case) and 120x (lower case) magnification showing the coating on a single bead.

Therapeutic protein-based drugs have great potential, and indeed insulin in a syringe has been around for decades. But a major hurdle that remains is that swallowing such drugs in pill form only adds to your dietary intake of protein. To actually get oral protein drugs to the bloodstream, and not its component amino acids, they need a coating that will prevent their digestion by the GI tract, but one that will dissolve in the small intestine and allow the drugs to be absorbed by the body.

Now researchers from Brown and Wayne State universities are reporting that a bioadhesive coating that sticks to the lining of the small intestine, called poly(butadiene-maleic anhydride-co-L-DOPA) (PBMAD), can ferry small plastic particles to stick to the small intestine and be absorbed in significantly higher concentrations than without the coating. Though plastic was used in the study on animal models to be able to follow the particles to their final destination, the technique holds promise for safe ferrying of proteins through the GI tract in a similar fashion.

Details from Brown:

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.

Study in Journal of Controlled Release: Can bioadhesive nanoparticles allow for more effective particle uptake from the small intestine?

Brown: Polymers key to oral protein-based drugs

Medgadget Editors

Medical technologies transform the world! Join us and see the progress in real time. At Medgadget, we report the latest technology news, interview leaders in the field, and file dispatches from medical events around the world since 2004.

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