This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: From vaccines to gene therapies, mRNA medicines often rely on tiny fat-based particles called lipid nanoparticles, or LNPs, to carry treatments where they need to go. But researchers still face a fundamental challenge: getting those therapies to the organs where they are needed most while limiting side effects elsewhere in the body.
Now, researchers at Georgia Tech and Emory University have discovered that delivering LNP medicines directly to various areas of the gastrointestinal (GI) tract—from the cheeks to the stomach to the rectum—could alter where the therapies travel in the body after being absorbed. This enables more precise targeting and opens new possibilities for mRNA therapies and vaccines. The study is published in the journal ACS Nano.
Several technologies are currently in development that enable oral and GI nucleic acid delivery, including pills, patches and endoscopic injections. "Here we show that oral delivery of mRNA wouldn't just enhance the patient experience compared to injections, but it also may enable improved or even completely new treatments," said Alex Abramson, an assistant professor in the School of Chemical and Biomolecular Engineering (ChBE). "We're able to deliver to organs that are hard to target via traditional administration methods while simultaneously reducing uptake in organs normally associated with toxicity." Typically, LNPs are delivered subcutaneously or intravenously, but that can mean the drugs affect more than just the intended target.
Drug interactions with organs such as the liver, lungs and spleen can cause unwanted side effects that limit how much medicine can be administered. The researchers found that delivering LNPs to different regions of the GI tract changed where the nanoparticles traveled in the body, allowing them to reach targets like the pancreas and lymph nodes while reducing targeting to the liver, lungs and spleen. "We found that the LNP was completely safe at a very high dose when delivered via a gastric route of administration," said Abdulraouf Abbas, a Ph.D. student in James Dahlman's Emory lab.
Dahlman is a McCamish Early Career Professor in the Department of Biomedical Engineering at Georgia Tech and Emory School of Medicine. "What's really exciting about not affecting the liver and the lungs is that it may allow us to increase the dose without increasing the side effects," Abramson said. Even better, if the goal is vaccination, the dose could be smaller because the therapy is delivered more directly to the desired target.
"Not only are we potentially improving LNP benefits by changing how it is administered, but we could even potentially decrease the cost of those mRNA vaccines or mRNA drugs," said Ramy Ghanim, a ChBE Ph.D. student. Using mouse models, the researchers mapped where nanoparticles traveled after microneedle injections delivered them to different parts of the GI tract. Once they identified which organs received the therapy, they could begin exploring potential medical applications.
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