Transepithelial Transport of Fc-Targeted Nanoparticles by the Neonatal Fc Receptor for Oral Delivery
2013.27.11
A new study published by Dr. Farokhzad and colleagues has demonstrated for the first time, the oral delivery of insulin-loaded nanoparticles across the transepithelial layer in the gut, using the neonatal Fc receptor (FcRn). In a paper published in the Nov. 27 online edition of Science Translational Medicine, the team showed the development and testing of biodegradable controlled release polymeric nanoparticles that have an antibody fragment on their surface, which targets the FcRn found on the surfaces of cells lining the intestines. This receptor mediates IgG antibody transport across epithelial barriers and was originally discovered as the receptor in the neonatal intestine that transports IgG in breast milk from the mother to her baby. Interestingly, this receptor is expressed into adulthood at similar levels to fetal expression and is an excellent targeting strategy — allowing the nanoparticles to get actively transported through the intestinal walls and enter the bloodstream. The team showed that nanoparticles coated with Fc proteins reached the bloodstream 11-fold more efficiently than equivalent nanoparticles without the coating. Furthermore, the amount of insulin delivered was large enough to lower the mice’s blood sugar levels. This type of drug delivery could be especially useful in developing new treatments for a range of diseases where regular medication is required. The lead authors of the study are Dr. Eric Pridgen (former MIT graduate now studying for his medical degree at Stanford University) and Dr. Frank Alexis (former BWH postdoctoral fellow now Assistant Professor at Clemenson University).
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