by Monash University

Credit: European Journal of Pharmaceutics and Biopharmaceutics (2024). DOI: 10.1016/j.ejpb.2024.114604

Researchers from the Monash Milk Team have published a new study demonstrating the power of human milk as a highly effective vehicle for administering certain medicines to infants.

In this preclinical study published in the European Journal of Pharmaceutics and Biopharmaceutics, the team found the amount absorbed of a medicine called clofazimine—its oral bioavailability—increased by more than 2.5-fold when administered with human milk.

Similarly, the oral bioavailability of clofazimine was significantly higher when administered in both human and bovine (cow) milk using a neonatal piglet model, suggesting comparable enhancement in oral bioavailability could be achieved with human or bovine milk.

Clofazimine has previously been used in the treatment of leprosy and is currently used to treat tuberculosis—the world's top infectious killer. In the context of this study, the researchers were testing how they could enhance the absorption of clofazimine among infants with the parasitic disease, cryptosporidiosis.

Cryptosporidiosis is responsible for significant diarrheal morbidity and mortality in under-5 children in low- and middle-income countries and in recent years clofazimine has been used as a treatment option in these settings.

The problem with using clofazimine for treating infants is that its effectiveness is limited by its inability to dissolve in our gastrointestinal contents. Human milk solves this problem by providing a favorable environment for the clofazimine to dissolve into, without needing other potentially toxic components to be included with the drug.

Professor Ben Boyd, one of the authors and head of the Monash Milk Team, which sits within the Monash Institute of Pharmaceutical Sciences (MIPS), said these findings further validate the enormous potential of milk-based vehicles to improve the oral bioavailability of medicines such as clofazimine, particularly among vulnerable infants where treatment options are limited.

"Through our research over the years, we've consistently been able to demonstrate the way in which certain medicines are able to 'piggyback' with the milk, which our body treats like food and digests," said Professor Boyd. "Through this process, the milk and drug are absorbed, thereby enhancing the effectiveness of the drug.

"In particular, we've been interested in how the delivery, absorption and overall therapeutic efficacy of poorly soluble medicines, such as clofazimine and some antimalarial medicines, can be enhanced in low-and middle-income settings where conventional forms of medicines are not suitable or available for infants."

The study's lead author and MIPS Ph.D. candidate, Ellie Ponsonby-Thomas, said the findings demonstrate the potential of human milk in particular to provide an effective way to administer medicines to infants without the need for additional pharmacological ingredients.

"Poorly soluble medicines such as clofazimine do not dissolve well in the stomach after administration and therefore developing age-appropriate formulations which are both safe and effective is challenging," she said.

"We know from previous studies that formulations aimed at infants involving milk-based vehicles can help medicines dissolve in the stomach, so we were excited to see this also applies to the administration of clofazimine."

The Monash Milk Team are trailblazers in understanding how milk and milk-like systems can be harnessed to enhance oral drug delivery. In 2020, they won a Eureka Prize for their innovative work in this space, including a study that demonstrated how infant formulas can be designed to enhance the solubilization of antimalarial medicines in children.

Subsequent preclinical studies have further validated the team's work, including this one which showed that cow's milk increases the oral bioavailability of cannabidiol (CBD) two-fold in pediatric patients experiencing harmful psychological conditions caused by epilepsy, along with this study which found that cow's milk increases the solubilization of the drug praziquantel (a poorly water soluble drug used to treat bacterial infections).

Although the positive effects of naturally derived milk on the performance of certain medicines are clear, using it as an effective way to enhance medicines is limited by several challenges in developing countries. This includes the need to refrigerate the milk prior to consumption and the variations in the quality of milk.

"Naturally derived milk presents many hurdles in developing countries which means that its implementation as an FDA-approved ingredient in medicines is difficult," Professor Boyd said.

"Therefore, finding a way to develop milk-based vehicles as low-cost, infant-friendly formulations, which are highly regulated in a food context, could provide alternative solutions for treating prevalent diseases in low-and middle-income countries."

The human milk used in the clofazimine study was generously donated to the Australian Red Cross Lifeblood by Australian mothers.

More information: Ellie Ponsonby-Thomas et al, Human milk improves the oral bioavailability of the poorly water-soluble drug clofazimine, European Journal of Pharmaceutics and Biopharmaceutics (2024). DOI: 10.1016/j.ejpb.2024.114604

Provided by Monash University