Researchers have developed a method to co-deliver potent drugs directly into a patient's cells, a method that could lead to more effective disease treatment.
The research, published in Advanced Materials, describes how ionizable drugs can be used to co-formulate siRNA for efficient intracellular delivery.
"We found that our co-formulation method not only potently delivered siRNA to cells but also simultaneously delivered active ionizable drugs," said Kai Slaughter, a Ph.D. candidate in Shoichet's lab. "This could be a game-changer for treating complex conditions where targeting multiple pathways is beneficial, such as cancer and viral infections."
In medicine, siRNA is a powerful tool capable of silencing the genes responsible for disease. However, siRNA is difficult to deliver into cells without degradation. While ionizable lipid design improvements have assisted in siRNA delivery efficiency, nanoparticle formulations are limited in the amount of drugs they can carry.
Often, when therapeutic formulations are absorbed by cells, the small molecule drugs and siRNA become trapped within endosomes, preventing them from reaching their target. The team discovered that by combining siRNA with ionizable drugs, the delivery efficiency and stability of the siRNA improves and can more effectively reach its target.
"One of the biggest hurdles in siRNA therapy has been getting these molecules to where they need to go without losing their potency," said Molly Shoichet, a professor at the University of Toronto Department of Chemical Engineering and Applied Chemistry. "Our approach using ionizable drugs as carriers marks a significant step forward in overcoming this barrier, while also showing how drugs and RNA can be delivered together in the same nanoparticle formulation."