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Scientists develop way to successfully give nanoparticle therapeutics orally

Boston, MA Pop a pill or be poked by a needle? Being able to orally deliver microscopic particlesknow as nanoparticlesloaded with medicine is a simple, convenient way to treat patients for various diseases, such as cancer or diabetes. But so far, nanoparticles can only be given via injection since they have trouble being readily absorbed by the intestine, which limits their usefulness.

Now a study led by researchers at Brigham and Women's Hospital (BWH) and Massachusetts Institute of Technology (MIT) is the first to report in the field of nanomedicine a new type of nanoparticle that can be successfully absorbed through the digestive tract. The findings may one day allow patients to simply take a pill instead of receiving injections.

The study will be published online November 27, 2013 in Science Translational Medicine.

The nanoparticles developed by the researchers are decorated with antibodies that attach to receptors found on the cell surfaces that line the intestines. Once attached, the nanoparticles gain entry past the cellular barriers in intestinal walls and into the bloodstream. According to the researchers, this type of drug delivery could also be useful in developing new treatments for conditions such as high cholesterol or arthritis.

"The novelty of actively being able to transport targeted nanoparticles across cell barriers can potentially open up a whole new set of opportunities in nanomedicine," said Omid Farokhzad, MD, director of the BWH Laboratory of Nanomedicine and Biomaterials, senior study author. "The body has receptors that are involved in shuttling proteins across barriers, as is the case in the placenta between the mother and fetus, or in the intestine, or between the blood and the brain. By hitching a ride from these transporters the nanoparticles can enter various impermeable tissues."

Until recently, after being injected into the body, nanoparticles travelled to their destination, such as a tumor, by seeping through leaky vessels. The research team, led by Farokhzad and Robert Langer, ScD of MIT, developed nanoparticles that could reach the target site without relying on injection nor leaky vessels.

For nanoparticles to be taken orally they need to cross the intestinal lining. This lining is composed of a layer of epithelial cells joined together to form impenetrable barriers called tight junctions. To ensure that the nanoparticles could cross these barriers, the researchers took a cue from research on how babies absorb antibodies from their mothers' milk. The antibodies would grab onto a receptor, known as neonatal Fc receptors, found on the cell surface. This gave them access across the cells of the intestinal lining into neighboring blood vessels.

Based on this knowledge, the researchers decorated nanoparticles with Fc proteins that targeted and bound to these receptors, which are also found in adult intestinal cells. After attaching to the receptors, the Fc-protein-decorated nanoparticlestoting their drug payloadare all absorbed into the intestinal lining and into the bloodstream at a high concentration.

According to the researchers, these receptors can be used to transport nanoparticles carrying different kinds of drugs and other materialsa feat that combines a versatile vehicle and an easily accessible passageway across cellular barriers.

To demonstrate how transport of Fc-targeted nanoparticles could impact the clinical space, the researchers focused on a diabetes treatment scenario, showing how oral delivery of insulin via these targeted nanoparticles could alter blood sugar levels in mice.

Insulin carried in nanoparticles decorated with Fc proteins reached the bloodstream more efficiently than those without the proteins. Moreover, the amount of insulin delivered was large enough to lower the mice's blood sugar levels. Aside from insulin, the researchers note that the nanoparticles can be used to carry any kind of drug to treat many diseases.

"Being able to deliver nanomedicine orally would offer clinicians broad and novel ways to treat today's many chronic diseases that require daily therapy, such as diabetes and cancer," said Langer. "Imagine being able to take RNA or proteins orally; that would be paradigm shift."

In terms of next steps, the researchers are working to enhance the nanoparticles' drug-releasing abilities to prepare for future pre-clinical testing with insulin and other drugs. They also plan to design nanoparticles that can cross other barriers, such as the blood-brain barrier, which prevents many drugs from reaching the brain.

"If you can penetrate the mucosa in the intestine, maybe next you can penetrate the mucosa in the lungs, maybe the blood-brain barrier, maybe the placental barrier," said Farokhzad.


Contact: Marjorie Montemayor-Quellenberg
Brigham and Women's Hospital

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