A combinatorial biomolecular strategy to identify peptides for improved transport across the sputum of cystic fibrosis patients and the underlying epithelia

Le résumé fourni par la source

Abstract Drugs and drug delivery systems have to traverse multiple biological barriers to achieve therapeutic efficacy. In diseases of mucosal-associated tissues such as cystic fibrosis (CF), successful delivery of gene and drug therapies remains a significant challenge due to an abnormally concentrated viscoelastic mucus, which prevents ~99% of all drugs and particles from penetrating the mucus barrier and the underlying epithelia for effective therapy, resulting in decreased survival. We used combinatorial peptide-presenting phage libraries and next-generation sequencing to identify hydrophilic, close to net-neutral charged peptides that penetrate the mucus barrier ex vivo in sputum from CF patients with ~600-fold better penetration than a positively charged control. After mucus penetration, nanoparticles conjugated with our selected peptides successfully translocated into lung epithelial cells derived from CF patients and demonstrated up to three-fold improved cell uptake compared to non-modified carboxylated- and gold standard PEGylated-nanoparticles. The selected peptides act as surface chemistries with synergistic functions to significantly improve the ability of drug delivery systems to overcome the human mucosal barriers and provide efficient cellular internalization. Our screening strategy provides a biologically-based discovery assay that directly addresses transport through mucus and cell barriers and has the potential to advance drug and gene delivery to multiple mucosal barriers.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.