2026-10-12T12:09:13Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34013737 2026-09-28T12:33:42Z category_1 category_4 category_146 category_7 category_14 category_19 category_21 category_873 category_734 portal_63 item_type_3 month_year_09_2026

Targeted Gastrointestinal Delivery of mRNA Lipid Nanoparticles Enables Systemic Vaccination and Glucagon-like Peptide‑1 Metabolic Therapy Abdulraouf M. Abbas (25122397) Ramy Ghanim (11521080) Sebastian Rudden (25122400) David Schultz (1753279) Bora Jang (5352638) Avraham Shakked (22360029) Hyejin Kim (587175) James E. Dahlman (1674883) Alex Abramson (25122403) Biophysics Biochemistry Space Science Medicine Molecular Biology Pharmacology Biotechnology Chemical Sciences not elsewhere classified Biological Sciences not elsewhere classified reprogram lnp biodistribution previously inaccessible locations ovalbumin mrna resulted multiple tissue types expanding therapeutic opportunities buffered saline controls enhancing lnp delivery targeted gastrointestinal delivery intramuscular delivery small intestinal results suggest mice compared lymphatic tissues like peptide intravenous administration given parenterally dosing mice Lipid nanoparticles (LNPs) administered parenterally often show poor localization to multiple tissue types, including the pancreas and gastrointestinal (GI) tract. Furthermore, patients typically prefer orally administered drugs to those that are given parenterally. We therefore investigated whether GI LNP administration to buccal, gastric, small intestinal, colonic, and rectal submucosal tissues could simultaneously circumvent parenteral administration while enhancing LNP delivery to previously inaccessible locations. We found that, in addition to local targeting, gastric LNP administration achieved an order of magnitude greater pancreas delivery in rodents than intravenous administration. Gastric dosing of glucagon-like peptide-1 mRNA also improved blood glucose regulation in mice compared with phosphate-buffered saline controls. Additionally, we found that buccal LNP administration targeted local and lymphatic tissues. Furthermore, dosing mice with ovalbumin mRNA resulted in equivalent immunoglobulin G blood titers to those of intramuscular delivery. These results suggest that GI administration can reprogram LNP biodistribution, expanding therapeutic opportunities for both local and systemic nucleic acid delivery. 2026-09-28T00:00:00Z Dataset Dataset 10.1021/acsnano.5c18549.s001 https://figshare.com/articles/dataset/Targeted_Gastrointestinal_Delivery_of_mRNA_Lipid_Nanoparticles_Enables_Systemic_Vaccination_and_Glucagon-like_Peptide_1_Metabolic_Therapy/34013737 CC BY-NC 4.0