When scientists design a new drug to treat disease, they must choose how patients will take the medicine: will it be a tablet, a syrup, an injection, or perhaps an ointment, an inhaler or a suppository? It’s a tricky decision. The human body has evolved physical and chemical barriers precisely to keep foreign substances out, so the dosage form is critical to ensure a drug reaches its target, without producing harmful effects elsewhere.
Nanoparticles offer a promising way to deliver new drugs, and a great opportunity to revamp old treatments by improving their safety and efficacy. These tiny structures range in diameter from 1 to 100 nanometres, which means even the biggest ones are about one thousand times smaller than a human cell. Crucially, the chemical and geometric properties of nanoparticles can be tuned to encapsulate medical compounds and carry them through the body to their place of action. Instead of flooding the gut or the bloodstream with medicine, this allows for more precise targeting and controlled release of the drug, even when it’s taken inside a pill.
Like New Deal, there are several other European projects — using very different compounds to treat very different ailments — which have all turned to nanoparticles for drug delivery. To administer immunosuppressors at a particular organ, for instance, nanocarriers are ideal, as they avoid a systemic (body-wide) weakening of the patient’s immune system. If the active compound is unstable, a nano formulation can also protect it from the body’s harsh environments. And for drugs with known toxicity at certain concentrations, nanoparticle delivery can minimise the dosage and the side-effects.
Packaged enzymes to treat a rare illness
Researchers in the Smart-4-Fabry project are working to achieve a nano formulation of the existing treatment for Fabry disease. People who suffer this rare genetic illness can’t properly produce an enzyme which digests large biomolecules known as sphingolipids. As a result, those molecules build up inside cells and blood vessels, leading to damage of the kidneys, heart and central nervous system, among other organs. Current treatment of Fabry disease involves intravenous injection of the required enzyme, α-Galactosidase A (GLA). The procedure has many drawbacks: the foreign enzymes can provoke an immune response in the patient, they’re unstable in the bloodstream, and they often hit a dead end when they reach cell membranes or other biological barriers.
Smart-4-Fabry scientists want to package GLA by surrounding the enzyme with a lipid membrane. The resulting nanoparticles should be able to deliver active GLA to all the cells that have built up harmful levels of sphingolipids. By using a nano-based delivery, patients receive the same active compound, but at lower doses — which the team hopes will reduce the appearance of drug resistance, minimise toxicity and lower the cost of treatment.
Inhalable nanoparticles aimed at the heart
Cupido is another European project applying nanoparticle delivery to existing drugs. In this case, it’s drugs for cardiovascular diseases, the biggest cause of death in the world. Most existing pharmacological treatments for the heart are administered orally or intravenously, allowing the compounds to circulate through the body and wreak far-ranging side-effects. Scientists and clinicians at Cupido think it’s time for “patient-friendly” therapies that work specifically on the heart.
They’ve come up with a change of tactic: inhalable nanoparticles. Their aim is to design tiny biocompatible and biodegradable capsules to encase drugs for cardiovascular disease, novel or available. Patients breathe in the particles using an inhaler — when they’ve reached the lungs, they pass into the bloodstream through the alveoli, and quickly translocate to the heart through the pulmonary vein. The idea is to design nanoparticles with chemical and magnetic properties that allow for a selective release of the enclosed drugs only at the target site. If all goes according to plan, this could be the first non-invasive and heart-specific therapy.
RNA parcels to penetrate the brain
The B-Smart project (Brain-Specific, Modular and Active RNA Therapeutics) looks into ways of targeting the brain, to get at the root causes of neurodegenerative diseases such as Alzheimer’s. Their approach is an answer to the available non-invasive treatments, which only act outside the brain and can therefore solely suppress symptoms. The main hurdle is posed by the specialised layers of cells which surround capillaries and regulate the entrance of substances from the bloodstream into the brain: the blood-brain barrier and the blood-cerebrospinal fluid barrier. Getting compounds past these strict borders is extremely difficult, but researchers at B-Smart are betting on nanoparticles to gain access.
They are testing a variety of different nanocarriers designed to protect RNA-based therapeutic compounds. This class of therapeutics acts by delivering instructions to the cells, in the form of single-stranded genetic molecules of RNA, which either interrupt or enhance the production of certain proteins. Some of the chosen nanocarriers are made from organic substances, such as lipids, while others are polymer-based. In all cases, carefully chosen molecules called targeting ligands line the surface of the particles, which enables them to bind — like a key to a lock — with specialised receptors on the brain’s border control cells. Binding of the nanocarriers at the barrier should facilitate uptake of their cargo, the therapeutic RNA, into the brain. From there, the molecule can act directly on diseased neurons. If successful, this approach of nanoparticle drug delivery could pave the way for treating other diseases that have a physiological basis in the brain.
Through these and other efforts, nanoparticles are slated to become a key asset in the pharmacologist’s toolkit: they are allowing scientists to consider the development of drugs previously deemed impractical, and they are offering safer and more effective delivery methods for existing therapeutic compounds.