Delivering medicine directly to the affected area provides direct access to the diseased area. Nanoparticles hold promise as a delivery method but are currently only available in injectable forms. Now, researchers from MIT and Brigham and Women’s Hospital have made a breakthrough by finding a way of delivering nanoparticles orally.
After the particles are intravenously injected into patients, they seep through the leaky blood vessels that typically surround tumors and diseased tissue, and release their payload at the tumor site.
But new research, published in Science Translational Medicine, is exploring alternatives to shots.
The researchers claim to have made breakthroughs that will smooth the way for the oral delivery of these “micro medicines.” They explain that oral administration has proved challenging in the past because it cannot travel across the intestinal epithelium into the bloodstream.
Senior author and director of the Laboratory of Nanomedicine and Biomaterials at Brigham and Women’s Hospital (BWH), Omid Farokhzad explains:
“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.”
Previous attempts to breach this barrier involved temporarily breaking them to allow drugs through. However, this approach is not without its dangers, as harmful bacteria can also get through.
The researchers revisited previous research that showed how babies absorb antibodies from their mother’s milk, boosting their own immune systems. In this case, the antibodies hook onto a cell surface receptor, known as FcRN, and this grants them access through the cell wall.
By coating nanoparticles with Fc proteins – the part of the antibody that binds to the receptor – the nanoparticles were simply piggybacked across with the FcRN.
And, as each nanoparticle – made of a biocompatible polymer called PLA-PEG – can carry a large drug payload at its core, this has wide-reaching implications.
Rohit Karnik, an MIT associate professor of mechanical engineering, explains:
“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.”
For the study, the researchers successfully demonstrated oral delivery of insulin in mice. They claim that the nanoparticles coated with Fc proteins entered the bloodstream “11-fold more efficiently than equivalent nanoparticles without the coating.” And the nanoparticles were able to transport enough insulin to lower the mice’s blood sugar levels.
The researchers are hopeful that by applying the same principles to designing nanoparticles, they will also be able to breach other barriers in the body, 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.”
This type of drug delivery could be especially useful in developing new treatments for conditions such as high cholesterol or arthritis. While patients may be reluctant to make frequent visits to a doctor’s office to receive a shot, they would be more likely to take nanoparticle pills regularly, say the researchers.
The researchers are now optimizing how the nanoparticles deliver drugs prior to testing on animals.