A sip instead of a shot: The future of drug delivery

Imagine if antibodies, proteins such as insulin, or even COVID-19 and flu vaccines could be consumed orally instead of via injection. This vision is closer than ever, according to a new study by Technion researchers published in the Journal of Controlled Release.

The study was led by Assistant Professor Assaf Zinger and Ph.D. candidate Si Naftaly from the Wolfson Faculty of Chemical Engineering at the Technion-Israel Institute of Technology. Their goal: to enable oral consumption of vaccines and medications, inspired by the unique properties of breast milk.

"Breast milk is a remarkable biofluid," explained Prof. Zinger, who received a prestigious ERC Starting Grant two years ago to develop artificial particles called "milkosomes" based on breast milk. "This fluid, which a baby consumes, contains a wide range of essential compounds. To impact the baby's health, these compounds must pass from the digestive system into the bloodstream by crossing the intestinal barrier."

The intestinal barrier is a large protective layer separating the inside of the intestine from the bloodstream. It consists of an epithelial cell layer and a mucus layer, acting as a crucial selective barrier that prevents harmful toxins from entering the bloodstream while allowing essential nutrients to pass through. "If compounds in breast milk can cross this barrier, it means breast milk contains 'keys' that enable them to do so," explained Si Naftaly. "What are these keys? That’s what we aimed to uncover in this study."

The Technion researchers’ paper reveals the answer through a phenomenon they discovered: the key to nanoparticle transport across the intestinal wall lies in breast milk proteins, which create an effect that named by the Technion scientists - Human Breast Milk Protein Corona. This "corona" forms a protein coating around the nanoparticle, allowing it to pass through the intestinal layers, and depends on the nanoparticles’ charge. The researchers confirmed their findings in both human intestinal cell line and pig intestinal samples.

Breast milk is the primary – and often the only – source of nutrition for newborns. It is a complex and dynamic fluid tailored to the infant’s needs, providing enzymes, growth factors, hormones, antibodies, nucleic acids, extracellular vesicles, carbohydrates, lipids (fat molecules), vitamins, minerals, and cells. These components are essential for brain development, immune system function, and microbiome balance in the digestive system.

Unlike formula, breast milk is not uniform; its composition varies significantly and is influenced by multiple maternal factors. In recent years, awareness of breast milk’s medical benefits has grown, and it is now recognized as a natural remedy for various conditions, particularly intestinal diseases.

Additional Insights:

• The research was a collaboration between Prof. Zinger and Prof. Maya Davidovich-Pinhas from the Faculty of Biotechnology and Food Engineering, alongside four students. Notably, one of the co-authors, Topaz Pery, joined the study as an undergraduate student in Prof. Zinger’s Lab in the Faculty of Chemical Engineering.
• The study compared breast milk, cow’s milk, and infant formula, revealing that breast milk exhibited the highest effect on the permeability of the intestinal barrier.
• Due to the events of October 7, most breast milk donations in Israel were allocated to orphans. As a result, the research team launched a local donation initiative within the Technion community to obtain the necessary samples.

The research was supported by the Israel Science Foundation, the Israel Cancer Research Fund, the Russell Berrie Nanotechnology Institute at the Technion, the Alon Fellowship, the Noam Seiden Fellowship for Nanotechnology and Optoelectronics, and an ERC "Milkosome" grant.

Assistant Prof. Assaf Zinger, a faculty member at the Wolfson Faculty of Chemical Engineering, is also a member of the Global Young Academy and a Fellow of the Royal Society of Chemistry. "I came to the Technion to conduct applied science," he said. "If it doesn’t make it to the clinic, it’s less interesting to me. When I recruit students, I ask them: Which excites you most – winning a Nobel Prize, becoming a multimillionaire, or saving lives? The third answer is a prerequisite for joining our lab."

Si Naftaly completed her B.Sc. and M.Sc. in biotechnology engineering at Ben-Gurion University, worked for four years at the biotech startup Ukko, and began her Ph.D. at the Technion in April 2022. In 2023, she helped organize the first International Student Conference for Chemical Engineering at the Technion and continues to volunteer in various initiatives.