So far nanoparticles where used for targeted treatment of cancer and other diseases and they have to be injeceted into patience.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 insted of receving injections.
They say that this new type of drug could be useful in developing new treatments for conditions such as high cholesterol or Arthrits. 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.
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.
The researchers’ discovery of how this type of particle can penetrate cells is a key step to achieving oral nanoparticle delivery, says Edith Mathiowitz, a professor of molecular pharmacology, physiology, and biotechnology at Brown University.
“Before we understand how these particles are being transported, we can’t develop any delivery system,” says Mathiowitz, who was not part of the research team.
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.
The researchers’ discovery of how this type of particle can penetrate cells is a key step to achieving oral nanoparticle delivery, says Edith Mathiowitz, a professor of molecular pharmacology, physiology, and biotechnology at Brown University.
“Before we understand how these particles are being transported, we can’t develop any delivery system,” says Mathiowitz, who was not part of the research team.
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