Researchers at Brigham and Women’s Hospital and Massachusetts Institute of Technology have achieved a breakthrough in nanomedicine by developing a new type of nanoparticle, which can be successfully absorbed through the digestive tract.
Researchers used the nanoparticles to demonstrate oral delivery of insulin in mice, but they reported that these particles could be used to transport different kinds of drugs and other materials 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 nanoparticles to pass through the intestinal walls and enter 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.
BWH Laboratory of Nanomedicine and Biomaterials director and senior study author Dr Omid Farokhzad said being able to transport targeted nanoparticles across cell barriers can potentially open up a whole new set of opportunities in nanomedicine.
"The body has receptors that are involved in shuttling proteins across barriers, as is the case in the placenta between the mother and foetus, or in the intestine, or between the blood and the brain," Dr Farokhzad said.
"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 tumour, by seeping through leaky vessels.
Led by Dr Farokhzad and Dr Robert Langer of MIT, the research team developed nanoparticles that could reach the target site without relying on injection or leaky vessels.
For nanoparticles to be taken orally they need to cross the intestinal lining, which 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 looked at 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 neighbouring blood vessels.
Using this knowledge, 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 nanoparticles with their drug payload were all absorbed into the intestinal lining and into the bloodstream at a high-concentration.
In the pursuit of next steps, the researchers are currently working to enhance the nanoparticles’ drug-releasing abilities to prepare for future pre-clinical testing with insulin and other drugs.
Researchers are also planning to design nanoparticles that can cross other barriers such as blood-brain, which prevents many drugs from reaching the brain.
This research was supported by the Koch-Prostate Cancer Foundation Award in Nanotherapeutics, the National Cancer Institute Center of Cancer Nanotechnology Excellence at MIT-Harvard; National Heart, Lung, and Blood Institute Programme of Excellence in Nanotechnology Award, as well as the National Institute of Health.