Packaging vitamin K in tiny spheres may help prevent serious bleeding in babies. Researchers at UMC Utrecht and the pharmaceutical company Tiofarma report in the journal Gastroenterology that they have taken an important step forward in developing this technology. This brings us one step closer to a possible alternative to vitamin K injections. ‘An injection has more advantages, but this is a good second option,’ says paediatrician specialising in metabolic diseases and researcher Peter van Hasselt (UMC Utrecht).
Vitamin K is essential for proper blood clotting. However, newborn babies often have low levels of vitamin K in their blood. During pregnancy, only limited amounts of this substance are transferred to the unborn child. To prevent vitamin K deficiency, newborn babies are therefore given extra vitamin K with their feed. However, this is not sufficient for babies who have difficulty absorbing fatty substances due to a liver problem. Vitamin K is a very fatty substance, and a deficiency can occur in babies with impaired fat absorption. The deficiency can lead to severe bleeding, including cerebral haemorrhages. Problems with fat absorption usually only become apparent once the bleeding has already occurred.
Vitamin K is currently administered via drops, but the effect of this is minimal. In the Netherlands, there are still relatively many cases of cerebral haemorrhages in babies. The Health Council therefore recommended administering vitamin K via injections. Last week, State Secretary Paul Blokhuis (Health, Welfare and Sport) announced that he would follow this advice. His decision means that from mid-2022, all newborns will receive a single vitamin K injection shortly after birth.
‘We are now showing that there are alternatives,’ says Thijs Rooimans, PhD candidate at Utrecht University. ‘People simply don’t like injections. Besides, it’s not always possible to administer injections.’
The absorption of vitamin K in the body is complex because it is an extremely fatty substance that dissolves poorly in water. It always needs an excipient to be absorbed properly. The excipient comes from bile, which is secreted in the intestine. The substance absorbs vitamin K in tiny spheres, also known as micelles. Thanks to the micelles, the body can absorb vitamin K. However, when fat absorption is disrupted, these aids are lacking. One solution would be to administer vitamin K and the aids orally in the form of micelles. But the problem is that the aids from the bile then suddenly must pass through the stomach, where stomach acids irreparably damage the micelles.
The researchers found two solutions to this problem. The first step was to “pre-package” vitamin K in micelles made from bile salts that also occur in our bodies. The researchers found a composition of bile salts that is resistant to stomach acid. Micelles of these bile salts remain intact in the stomach and deliver the packaged vitamin K to the intestines. In addition, they applied a kind of molecular garland to the outside of the micelles, which prevents the micelles from clumping together.
In the journal Gastroenterology, the researchers demonstrate that their approach works in laboratory animals with impaired fat absorption. ‘Individually, both solutions are about equally effective,’ says Peter van Hasselt. ‘But when you combine the two, the absorption of vitamin K in the body becomes more stable and reliable. It is sufficient to achieve relevant vitamin K levels in the blood.’
According to the researchers, their method also offers good prospects for other lipid-based drugs. ‘We are now investigating whether the same approach will work for an anti-cancer drug,’ says Rene van Nostrum, affiliated with Utrecht University. ‘Can we encapsulate the drug, will it remain stable, and will the micelles reach the intestines?’
Van Hasselt: ‘There are still many fatty drugs in the pipeline. They are not yet reaching the final stage of development because they are difficult to get into the body. So it makes sense to see whether this method can also be used for this group of drugs.’
Read the publication in Gastroenterology