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Gastrointestinal delivery of mRNA lipid nanoparticles selectively targets the pancreas

Abbas, A. M.; Ghanim, R.; Rudden, S.; Schultz, D.; Shakked, A.; Kim, H.; Dahlman, J.; Abramson, A.

2025-09-18 bioengineering
10.1101/2025.09.15.676190 bioRxiv
Show abstract

Lipid nanoparticles (LNPs) administered parenterally often show poor localization to the gastrointestinal (GI) tract and pancreas. In addition, patients typically prefer orally administered drugs to those given intravenously. We therefore investigated whether GI delivery, achievable via device mediated microneedle injections applied to buccal, gastric, small intestinal, colonic, or rectal tissues, could simultaneously enhance LNP delivery to the GI and pancreas while avoiding intravenous administration. Using a combined approach of formulation optimization and GI delivery site screening, we found that cationic SM-102 LNPs delivered gastrically achieved 7-fold higher pancreas delivery in rodents than intravenous neutral SM-102 LNPs. With dose optimization, gastric LNPs achieved 6000-fold greater pancreas to liver targeting ratios than intravenous LNPs. These results suggest GI microneedle administration can reprogram LNP biodistribution, thereby expanding therapeutic opportunities for both local and systemic nucleic acid delivery.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.