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Dec 19, 2013
 |  BC Innovations  |  Cover Story

Oral nanoparticles

Researchers from Brigham and Women's Hospital and the Massachusetts Institute of Technology have developed targeted nanoparticles that could enable the oral delivery of biologics such as insulin.1 The clinical translation of the approach will require identifying a suitable therapeutic payload and fine-tuning the pharmacology of the system.

Poor intestinal absorption prevents the oral delivery of many compounds and virtually all biologics. Factors that affect oral bioavailability include stability and size, as peptide therapeutics generally are degraded in the GI tract and large molecules cannot be passively absorbed through the intestinal epithelium.

Several companies have tried to develop oral delivery methods for biologics. In 2006, an oral insulin tablet from Emisphere Technologies Inc.

failed in a Phase II trial in type 2 diabetes. In 2011, Emisphere and partners Nordic Bioscience A/S and Novartis AG discontinued development of the oral salmon calcitonin biologic SMC021 after it failed several Phase III trials in osteoarthritis and osteoporosis.

Emisphere is now using its Eligen oral drug delivery platform, which consists of binding small molecules to the therapeutic of interest to facilitate its passive transport into the cells, to develop oral formulations of Novo Nordisk A/S' glucagon-like peptide-1 (GLP-1) analogs for diabetes.

Altus Biologics Inc. discontinued development of the oral cross-linked pancreatic enzyme crystal biologic Trizytek liprotamase, which was in development to treat malabsorption caused by exocrine pancreatic insufficiency in patients with cystic fibrosis (CF). The company, which was creating oral biologics using the cross-linked enzyme crystal protein technology platform, filed for bankruptcy in 2009 and was acquired by Althea Technologies Inc. in 2010.

Omid Farokhzad and colleagues at Brigham and Women's Hospital decided to tackle oral biologics by marrying a drug-stabilizing approach with a method for improving the uptake of biologics. Farokhzad is an associate professor of anesthesia at Brigham and Women's Hospital.

For stability, the team opted for nanoparticles that encapsulate compounds or peptides. For uptake, the group chose to target neonatal Fc fragment of IgG receptor transporter-α (FCGRT; FCRN).2,3 FCRN normally functions to transport maternal IgG from...

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