Scientists are working on a new kind of pill loaded with microscopic drug capsules that can safely pass through the intestinal wall.
Early tests have already shown how one oral nanoparticle containing insulin can reduce blood sugar levels in mice.
Currently, diabetics lacking the hormone have to self-inject it, sometimes several times a day.
The development of an insulin pill would transform the management of Type 1 diabetes.
Future nanoparticle pills may also be used to deliver drugs across other natural barriers surrounding the brain, lungs and placenta.
"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," said Professor Robert Langer, a member of the research team from the Massachusetts Institute of Technology (MIT) in Boston, US.
"Imagine being able to take RNA or proteins orally; that would be paradigm shift."
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Nanoparticles are being actively explored by numerous research groups as "smart" drug delivery systems that could be designed to target specific cells, or time the release of medicines.
Typically they consist of tiny spheres of synthetic material holding the desired medication within a hollow core, or dispersed throughout the particle body, or attached to its surface. By definition, a nanoparticle is an object up to a millionth of a millimetre across.
Until now, nanoparticles have only been considered as injectible treatments because of their inability to penetrate the cellular barrier lining the gut.
Scientists solved the problem by mimicking the way babies absorb antibodies from their mothers' milk to boost their immune systems.
The antibodies attach onto "receptor" molecules on the intestinal wall cell surface that act like gates, allowing access to adjacent blood vessels.
Taking a cue from nature, the researchers decorated their nanoparticles with proteins that the target the same receptors. Once the protein unlocks the receptor gate, the whole nanoparticle and its payload is allowed through.
"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 study leader Dr Omid Farokhzad, director of the Brigham and Women's Hospital Laboratory of Nanomedicine and Biomaterials in Boston.
"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. By hitching a ride from these transporters, the nanoparticles can enter various impermeable tissues."
The mouse experiments showed that nanoparticles administered by mouth could deliver enough insulin to lower the animals' blood sugar levels.
Theoretically, the same technique could be used to deliver a vast array of drugs to treat many different diseases, said the researchers whose findings appear in the journal Science Transitional Medicine.
They are now working to enhance the nanoparticles' drug-releasing abilities and prepare for more laboratory tests with insulin and other drugs. There are also plans to design nanoparticles capable of crossing other barriers, such as the blood-brain barrier that prevents many kinds of drug from entering 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," said Dr Farokhzad.
Patients are much more likely to stick to a treatment regime that involves pills rather than injections, the scientists point out.
"If you were a patient and you had a choice, there's just no question: patients would always prefer drugs they can take orally," Prof Langer added.
Several types of nanoparticle carrying chemotherapy drugs or "interfering" RNA molecules that switch off selected genes are now in clinical trials to investigate their potential for treating cancer and other diseases.
They exploit the fact that tumours and other diseased tissues are surrounded by leaky blood vessels. After being intravenously injected, the particles pass through the leaky vessels and release their drug cargoes.
Previous attempts have been made to force nanoparticles through the gut wall by temporarily disrupting the so-called "tight junctions" that seal together intestinal lining cells. But this runs the risk of also allowing access to unwanted intruders, such as bacteria.
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