Now, researchers from MIT and Brigham and Women's Hospital (BWH) have developed a new type of nanoparticle that can be delivered orally and absorbed through the digestive tract, allowing patients to simply take a pill instead of receiving injections.
In a paper appearing in the Nov. 27 online edition of Science Translational Medicine, the researchers used the particles to demonstrate oral delivery of insulin in mice, but they say the particles could be used to carry any kind of drug that can be encapsulated in a nanoparticle. The new nanoparticles are coated with antibodies that act as a key to unlock receptors found on the surfaces of cells that line the intestine, allowing the nanoparticles to break through the intestinal walls and enter the bloodstream.
This type of drug delivery could be especially useful in developing new treatments for conditions such as high cholesterol or arthritis. Patients with those diseases would be much more likely to take pills regularly than to make frequent visits to a doctor's office to receive nanoparticle injections, say the researchers.
"If you were a patient and you had a choice, there's just no question: Patients would always prefer drugs they can take orally," says Robert Langer, the David H. Koch Institute Professor at MIT, a member of MIT's Koch Institute for Integrative Cancer Research, and an author of the Science Translational Medicine paper.
Lead authors of the paper are former MIT grad student Eric Pridgen and former BWH postdoc Frank Alexis, and the senior author is Omid Farokhzad, director of the Laboratory of Nanomedicine and Biomaterials at BWH. Other authors are Timothy Kuo, a gastroenterologist at BWH; Etgar Levy-Nissenbaum, a former BWH postdoc; Rohit Karnik, an MIT associate professor of mechanical engineering; and Richard Blumberg, co-director of BWH's Biomedical Research Institute.
No more injections
Several types of nanoparticles carrying chemotherapy drugs or short interfering RNA, which can turn off selected genes, are now in clinical trials to treat cancer and other diseases. These particles exploit the fact that tumors and other diseased tissues are surrounded by leaky blood vessels. After the particles are intravenously injected into patients, they seep through those leaky vessels and release their payload at the tumor site.
For nanoparticles to be taken orally, they need to be able to get through the intestinal lining, which is made of a layer of epithelial cells that join together to form impenetrable barriers called tight junctions.
"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 says.
Researchers have previously tried to break through this wall by temporarily disrupting the tight junctions, allowing drugs through. However, this approach can have unwanted side effects because when the barriers are broken, harmful bacteria can also get through.
To build nanoparticles that can selectively break through the barrier, the researchers took advantage of previous work that revealed how babies absorb antibodies from their mothers' milk, boosting their own immune defenses. 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.
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," Karnik says.
Breaking through barriers
In this study, the researchers demonstrated oral delivery of insulin in mice. Nanoparticles coated with Fc proteins reached the bloodstream 11-fold more efficiently than equivalent nanoparticles without the coating. Furthermore, the amount of insulin delivered was large enough to lower the mice's blood sugar levels.
The researchers now hope to apply the same principles to designing 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," Farokhzad says.
They are also working on optimizing drug release from the nanoparticles in preparation for further animal tests, either with insulin or other drugs.
The research was funded by a Koch-Prostate Cancer Foundation Award in Nanotherapeutics; the National Cancer Institute Center of Cancer Nanotechnology Excellence at MIT-Harvard; a National Heart, Lung, and Blood Institute Program of Excellence in Nanotechnology Award; and the National Institute of Biomedical Imaging and Bioengineering.
Written by Anne Trafton, MIT News Office
Sarah McDonnell | EurekAlert!
When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short
23.03.2017 | Institut für Pflanzenbiochemie
WPI team grows heart tissue on spinach leaves
23.03.2017 | Worcester Polytechnic Institute
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
23.03.2017 | Life Sciences
23.03.2017 | Power and Electrical Engineering
23.03.2017 | Earth Sciences