November 28, 2013
Newly-Developed, Antibody-Laced Nanoparticles Could Be Delivered Orally
redOrbit Staff & Wire Reports - Your Universe Online
Researchers from MIT and Brigham and Women's Hospital (BWH) have developed a new type of nanoparticle that can be absorbed through the digestive tract, bringing the cutting-edge treatment method one-step closer to being administered orally instead of through injections.
While drugs delivered by nanoparticles could help treat cancer, diabetes and several other types of disease, the fact that these particles currently have to be injected into patients has thus far limited how useful they can be. However, in a new study published in Thursday’s online edition of the Science Translational Medicine, the authors explain how they have come one step closer to overcoming that particular obstacle.
Dr. Omid Farokhzad, senior author and director of the BWH Laboratory of Nanomedicine and Biomaterials, and his colleagues developed nanoparticles that have been decorated with antibodies, the hospital explained in a statement. Those antibodies attach to receptors on the surfaces of intestinal cells, and once attached, the nanoparticles can maneuver past the cellular barriers into the bloodstream.
The study authors claim that this drug delivery method could aid in the development of new medications for the treatment of arthritis or high cholesterol. It would be easier for individuals suffering from those conditions to regularly take pills than to frequently visit the doctor’s office to receive nanoparticle injection treatments, they noted.
“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 Dr. Farokhzad. “The body has receptors that are involved in shuttling proteins across barriers, as is the case in the placenta… in the intestine, or between the blood and the brain. By hitching a ride from these transporters the nanoparticles can enter various impermeable tissues.”
“If you were a patient and you had a choice, there's just no question: Patients would always prefer drugs they can take orally,” added MIT professor and study author Robert Langer. “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.”
There are several types of nanoparticle treatments currently in the works, and this method exploits the fact that diseased tissues and tumors are typically surrounded by leaky blood vessels. Once the particles are injected into patients, they seep through those blood vessels and administer their medication at the target site. For these medications to be given orally, they would first have to be able to penetrate the intestinal lining.
“The key challenge is how to make a nanoparticle get through this barrier of cells. Whenever cells want to form a barrier, they make these attachments from cell to cell, analogous to a brick wall where the bricks are the cells and the mortar is the attachments, and nothing can penetrate that wall," Farokhzad said.
Previously, scientists have attempted to surpass this wall of epithelial cells by causing a temporary disruption in these seemingly impenetrable barriers so that the drugs could pass through. However, this technique could also allow harmful bacteria to pass through, potentially resulting in unwanted side effects. This new method builds on previous research that revealed how babies absorb antibodies from mothers' milk to boost their immune systems.
“Those antibodies grab onto a cell surface receptor called the FcRN, granting them access through the cells of the intestinal lining into adjacent blood vessels,” MIT explained in a statement. “The researchers coated their nanoparticles with Fc proteins – the part of the antibody that binds to the FcRN receptor, which is also found in adult intestinal cells. The nanoparticles, made of a biocompatible polymer called PLA-PEG, can carry a large drug payload, such as insulin, in their core. After the particles are ingested, the Fc proteins grab on to the FcRN in the intestinal lining and gain entry, bringing the entire nanoparticle along with them.”
“It illustrates a very general concept where we can use these receptors to traffic nanoparticles that could contain pretty much anything. Any molecule that has difficulty crossing the barrier could be loaded in the nanoparticle and trafficked across,” added Rohit Karnik, an MIT associate professor of mechanical engineering and one of the lead authors of the paper.