Researchers from the College of Agricultural Sciences at Pennsylvania State University say they have found a way to deliver an antiretroviral drug to infants and young children through a baby formula – a method that could significantly improve treatment for the 3.2 million children worldwide living with HIV.
The research team, including Frederico Harte, associate professor of food science at Penn State, publish their findings in the journal Pharmaceutical Research.
Around 90% of children with human immunodeficiency virus (HIV) live in sub-Saharan Africa, where there is limited access to antiretroviral treatments. According to the World Health Organization (WHO), only 23% of these children received antiretroviral medication last year.
But even when children are able to access this medication, they may not respond well to it. Harte notes that Ritonavir – one of the most commonly used antiretroviral drugs to prevent and treat HIV and acquired immune deficiency syndrome (AIDS) – can cause a number of side effects, such as diarrhea, vomiting, stomach pain and weakness.
Harte says it can also be difficult to administer the drug to infants. “The liquid formulation used to treat infants over 1 month of age contains 43% ethanol and has an awful flavor that has been described as bitter-metallic, medicinal, astringent, sour and burning,” he explains.
Furthermore, the drug is not absorbed easily. “Ritonavir has a high hydrophobicity and low solubility in water,” says Harte, “which lead to a low dissolution rate in the gastrointestinal fluid and, hence, to insufficient bioavailability.”
As such, Harte and colleagues set out to find a more effective way to deliver this drug to children, while ensuring it can be easily dissolved in the gut.
For their study, the team investigated a group of proteins called caseins, which are found in cow’s milk.
Casein proteins produce casein micelles – particles that are behind milk’s white color. Casein micelles are responsible for delivering calcium and amino acids in milk from a mother to their young. This got the team thinking: could casein micelles deliver Ritonavir molecules, too?
“I have been working with bovine casein micelles for a few years now, and we have investigated the structure and functionality of these proteins,” says Harte. “What we found is these micelles are able to carry molecules that have very little solubility in water, that have low molecular weight and that are very hydrophobic – such as Ritonavir.”
What is more, the team found that they could alter the casein micelles to boost their binding properties, meaning they could attach Ritonavir molecules to the micelles more effectively. They did this by homogenizing cow’s milk at 400-500 megapascals. For comparison, Harte notes that milk is normally homogenized at 10-15 megapascals.
Explaining what these findings mean, Harte says:
“As a result of this enhanced binding of molecules, we believe a milk powder containing Ritonavir can be used as baby formula, providing a transport system for a drug that is not very soluble in water.”
The researchers say they are currently in the process of testing this formula on three piglets, and blood samples are being taken from the animals every 3 hours to assess its effectiveness.
“The hope is that – and we don’t have the data yet – we find that the Ritonavir is being adequately delivered by the protein in milk,” says Harte. “So if that works, I think we are pretty close to having a formulation that can be used with hydrophobic drugs.”
He adds that he is hopeful their findings will lead to a new drug delivery system to protect against and treat HIV and AIDS, but he notes that the formula needs to be tested in clinical trials to know for certain.
Last month, Medical News Today reported on a study revealing that – for the first time – researchers have developed technologies that allow them to watch how HIV proteins move on the surface of the virus in real-time.
According to the researchers of that study, the discovery may help understanding of how HIV infects human cells, opening the door to new prevention strategies.