In a development that could transform treatment for millions suffering from inflammatory bowel diseases, researchers at Tel Aviv University have discovered how to deliver medication directly to the intestines while bypassing the liver – a longstanding challenge in drug development. The breakthrough involves a clever manipulation of the tiny fat particles that carry therapeutic molecules through the bloodstream.
“Everything injected into the bloodstream eventually ends up in the liver — that’s just how our anatomy works,” explains Professor Dan Peer, Vice President for R&D at Tel Aviv University and Director of the Laboratory of Precision Nano-Medicine at the Shmunis School of Biomedical and Cancer Research. “This poses two challenges. First, drugs intended to target specific cells in particular organs may be toxic to the liver. Second, we don’t want drugs to get ‘stuck’ in the liver.”
The research team altered the composition of lipid nanoparticles – the same technology used in COVID-19 vaccines – to create a form of molecular transportation that naturally flows toward intestinal tissue. By increasing the proportion of a specific fat molecule called phospholipid from 10% to 30%, they were able to direct therapeutic molecules straight to their target.
“That’s the whole trick,” notes Peer. “We adjusted the lipid composition and found that at 30% phospholipid, the drug is directed straight to the intestine. This wasn’t a blind trial-and-error approach. We understand the mechanism, at least partially, and recognize that this ratio more closely resembles a natural biological membrane, which intestinal cells are better suited to absorb.”
The researchers demonstrated their method’s effectiveness by successfully delivering an anti-inflammatory protein to treat Crohn’s disease and colitis in animal models. The approach not only delivered the therapeutic molecules to the inflamed intestine but also transformed immune cells there into factories producing anti-inflammatory compounds.
This development represents more than just a new drug delivery method. It offers a potential paradigm shift in how medications could be targeted to specific organs. The team is now exploring ways to adapt their technique to target other organs like the pancreas, which has traditionally been difficult to reach with conventional drug delivery methods.
The implications extend far beyond inflammatory bowel diseases. By fine-tuning the composition of these lipid nanoparticles, researchers might be able to create precisely targeted treatments for a wide range of conditions that affect specific organs, potentially reducing side effects and improving treatment efficacy.
The study, published in Advanced Science, opens new possibilities for developing treatments that can reach their intended targets more efficiently than ever before. As Professor Peer notes, “This direct delivery method for mRNA drugs opens up broad possibilities for developing new and more precise therapies than ever before.”
The research was led by post-doctoral fellow Dr. Riccardo Rampado in collaboration with Professor Peer, whose laboratory has been pioneering developments in mRNA therapeutics. Their findings suggest that sometimes the most significant breakthroughs come not from developing new drugs, but from finding smarter ways to deliver existing ones.