Mucus-penetrating peptides with companion screening assay

Novel nanoparticle carriers allow for drug delivery through mucosal barriers

Description

Mucosal barriers surround the eyes, lungs, and GI tract. These mucosal barriers keep foreign particles out, protecting against infectious agents and allergens. Unfortunately, this mucosal barrier also creates an obstacle for delivering therapeutic agents. This therapeutic challenge is most pronounced in cystic fibrosis (CF), where the mucus in the lung is thicker, dryer, and stickier compared to healthy patients. In CF, the mucus layer prevents up to 91% of model drugs and 99% of polymeric nanoparticles from penetration needed for successful therapy.1,2 Traversing the mucosal barrier is a critical bottleneck that is hindering drug development for cystic fibrosis.3

The Ghosh Lab at UT Austin has coupled emerging biotechnologies like phage display and next-gen sequencing to design peptide based nanocarriers that can shuttle drugs across the CF mucosal barrier. The research group identified a group of peptides that significantly improved the diffusion of nanoparticles through the sputum of CF patients. The physical properties of the CF mucus can vary from patient to patient. It was discovered that a few key physical properties like negative to neutral net-charge and hydrophilic sequences enhance diffusion across samples from a variety of CF patients.4,5 Importantly, these constructs exhibited three-fold higher cell uptake compared to gold standard polymeric nanoparticles. These peptide carriers have the properties needed to get drugs across the mucosal barrier and into the epithelial cells of the lung. These peptide carriers create exciting opportunities for new therapeutics with enhanced mucosal delivery.

References

1.  Bhat, P.G. et al., J. Pharm. Sci., 85 (1996), pp. 624-630. https://doi.org/10.1021/js950381s

2.  Tang, B.C. et al., Proc. Natl. Acad. Sci., 106 (2009), pp. 19268-19273. https://doi.org/10.1073/pnas.0905998106

3.  Leal, J. et al., Int J Pharm Oct 30;532(1):555-572. https://doi.org/10.1016/j.ijpharm.2017.09.018.

4.  Leal J. et al., 2018 Int J Pharm. 2018 Dec 20;553(1-2):57-64. https://doi.org/10.1016/j.ijpharm.2018.09.055

5.  Leal J. et al., J. Contr. Release Volume 322, 10 June 2020, pages 457-469 2018 https://doi.org/10.1016/j.jconrel.2020.03.032