Research ArticleNanomedicine

Transepithelial Transport of Fc-Targeted Nanoparticles by the Neonatal Fc Receptor for Oral Delivery

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Science Translational Medicine  27 Nov 2013:
Vol. 5, Issue 213, pp. 213ra167
DOI: 10.1126/scitranslmed.3007049

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A Spoonful of Nanomedicine

Oral delivery of drug-loaded nanoparticles is, to some, the Holy Grail of nanomedicine. Patients can easily pop a pill, which makes them more compliant with a therapeutic regimen. The difficulty with ingesting these tiny particles is that they are not readily absorbed in the intestine, thus eliminating most of the particles from the body and, in turn, limiting efficacy. In response, Pridgen et al. designed polymeric nanoparticles targeting a receptor expressed on the surface of the intestine to actively transport the particle across the cell into the patient’s circulation.

The nanoparticles were decorated with Fc fragments that readily bind to the neonatal Fc receptor (FcRn) in the intestinal epithelium. The authors observed that the Fc-targeted nanoparticles crossed the intestinal barrier both in vitro, using human epithelial cells, and in vivo in mice (who also express FcRn), ending up in high concentrations in several organs of the body. By contrast, nontargeted nanoparticles were barely visible. To demonstrate the therapeutic benefits of these Fc-targeted nanoparticles, Pridgen et al. administered insulin-laden targeted and nontargeted particles orally to mice. Free insulin given orally did not generate a glucose response in the animals, similar to the nontargeted, insulin-containing particles. However, Fc-targeted nanoparticles containing insulin produced a significant hypoglycemic response in the mice. To confirm that the targeting and epithelial transport is important for this mode of delivery, the authors showed that animals lacking FcRn did not respond to the insulin-filled Fc-targeted nanoparticles.

The ability to deliver nanomedicine orally would open doors to treating many chronic diseases that require daily therapy, such as diabetes and cancer. This study by Pridgen et al. is an exciting proof of concept but will require longer periods of testing in disease models to confirm that FcRn targeting is essential and safe for human use.

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