Transepithelial Transport of Fc-Targeted Nanoparticles by the Neonatal Fc Receptor for Oral Delivery
Year: 2013
Type: article
Abstract: Nanoparticles are poised to have a tremendous impact on the treatment of many diseases, but their broad application is limited because currently they can only be administered by parenteral methods. Oral administration of nanoparticles is preferred but remains a challenge because transport across the intestinal epithelium is limited. We show that nanoparticles targeted to the neonatal Fc receptor (FcRn), which mediates the transport of immunoglobulin G antibodies across epithelial barriers, are efficiently transported across the intestinal epithelium using both in vitro and in vivo models. In mice, orally administered FcRn-targeted nanoparticles crossed the intestinal epithelium and reached systemic circulation with a mean absorption efficiency of 13.7%*hour compared with only 1.2%*hour for nontargeted nanoparticles. In addition, targeted nanoparticles containing insulin as a model nanoparticle-based therapy for diabetes were orally administered at a clinically relevant insulin dose of 1.1 U/kg and elicited a prolonged hypoglycemic response in wild-type mice. This effect was abolished in FcRn knockout mice, indicating that the enhanced nanoparticle transport was specifically due to FcRn. FcRn-targeted nanoparticles may have a major impact on the treatment of many diseases by enabling drugs currently limited by low bioavailability to be efficiently delivered though oral administration.
Source: Science Translational Medicine
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: green
Funders: Prostate Cancer Foundation, National Institutes of Health, National Defense Science and Engineering Graduate, Harvard Digestive Diseases Center, Harvard University, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Biomedical Imaging and Bioengineering
Awards: Controlled Release of Macromolecules, G1780665944, G1786187041, G2788177171, G3093553694, G389456503, G397724349, A new high-throughput gastrointestinal tract explant platform for drug formulation discovery and metabolic disease modulation, MIT-Harvard Center of Cancer Nanotechnology Excellence, Intestinal Immune Regulation by IgG and FcRn, G517097443, Development of FcRn-Targeted Nanoparticles for Efficient Oral Delivery of Insulin, G5797641063, Intestinal Immune Regulation by IgG and FcRn, G6632036768, G7185013638, G9000010315, G9000084514, G9000163483, G9000231428, G9000340342, Integrated Epithelial and Muscosal Biology
OpenAlex ID: W2145756312