Espicom View: Nanoparticles have had a significant impact on the treatment of a number of diseases, but their application has been limited, due to the fact that they can only be administered via parenteral methods. Oral administration of nanoparticles is preferable, but has historically been challenging, because transport across the intestinal epithelium is limited. BIND Therapeutics offers an oral delivery method, and while still preclinical, the publication of this research is good news for BIND Therapeutics, demonstrating that its nanoparticle technology can successfully cross a number of biological barriers. As a recently publicly listed company, BIND Therapeutics' shares rose by 4.2% on November 27, the day the company announced the publication of this data. Investors seem to be optimistic that this biotech company is one to watch.
BIND Therapeutics, a clinical-stage nanomedicine platform company developing targeted and programmable therapeutics called Accurins, has published data demonstrating the successful engineering of targeted nanoparticles to cross biological barriers, such as the intestinal barrier, and enter the bloodstream, potentially broadening future therapeutic applications for BIND's medicinal nanoengineering platform.
In a paper entitled, 'Transepithelial Transport of Fc-Targeted Nanoparticles by the Neonatal Fc Receptor for Oral Delivery', published in the November 27 2013 online issue of Science Translational Medicine, researchers at the Massachusetts Institute of Technology David Koch Institute for Integrative Cancer Research and Brigham & Women's Hospital/Harvard Medical School, including BIND's co-founders Robert Langer and Omid Farokhzad, demonstrated the ability to enhance the surface properties of the nanoparticle to target the neonatal Fc receptor (FcRn), a transport receptor present on the plasma membrane of cells that form many of the biological barriers in the body including: intestinal epithelial barrier, pulmonary epithelial barrier, blood-brain barrier, foetal-placental barrier and blood-ocular barrier.
The FcRn function is to shuttle immunoglobulin G (IgG) molecules across biological barriers that are otherwise impermeable to IgG. Taking advantage of the biological properties of the FcRn as a model transcellular trafficking receptor, the investigators demonstrated for the first time, proof of concept in a preclinical model that targeted therapeutic nanoparticles can exploit biological transport pathways and gain access to biological compartments that are otherwise impermeable to nanoparticles and other macromolecules. The FcRn-targeted nanoparticles were shown in an animal model to cross the intestinal epithelial barrier after oral administration and enter the systemic circulation, displaying an absorption efficiency that enabled uptake of therapeutic dose levels. As expected, the FcRn-mediated nanoparticle absorption was lost in animals deficient in FcRn expression. Using insulin as a model large molecular weight drug with minimal oral bioavailability, the FcRn-targeted nanoparticles were able to significantly increase insulin bioavailability resulting in plasma glucose modulation.
BIND has used its medicinal nanoengineering platform to produce a pipeline of Accurins, including its proprietary lead drug candidate, BIND-014, currently in Phase II clinical trials in non-small cell lung cancer and metastatic castrate-resistant prostate cancer, and partnered Accurins through collaborations initiated in 2013 with Amgen, Pfizer and AstraZeneca. The current findings are expected to significantly broaden the reach of BIND's platform and present opportunities to non-invasively administer Accurins of large molecular weight drugs, such as proteins and RNA, for a myriad of human diseases.
Biological barriers present in the human body, such as the intestinal epithelial lining, the blood-brain barrier and the mucosa of the lungs and eyes, have hindered absorption of nanoparticles. By targeting the neonatal FcRn, BIND has demonstrated the ability to engineer targeted therapeutic nanoparticles that cross biological barriers and enter the bloodstream at therapeutic levels, which could pave the way for opportunities for Accurins therapeutics other biological applications.