title: Cell-penetrating peptides as tools to enhance non-injectable delivery of biopharmaceuticals.
abstract: Non-injectable delivery of peptide and protein drugs is hampered by their labile nature, hydrophilicity, and large molecular size; thus limiting their permeation across mucosae, which represent major biochemical and physical barriers to drugs administered via e.g. the oral, nasal, and pulmonary routes. However, in recent years cell-penetrating peptides (CPP) have emerged as promising tools to enhance mucosal delivery of co-administered or conjugated peptide and protein cargo and more advanced CPP-cargo formulations are emerging. CPPs act as transepithelial delivery vectors, but the mechanism(s) by which CPPs mediate cargo translocation across an epithelium is so far poorly understood; both due to the fact that multiple factors influence the resulting uptake and trafficking mechanisms as well as to the complicated nature of sensitive studies of this. In addition to a proper mechanistic understanding, documentation of CPP-mediated delivery in higher animal species than rodent as well as extensive toxicological studies are necessary for CPP-containing non-injectable DDSs to reach the clinic.
authors.affiliation: Department of Pharmacy, Section for Biologics, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark.
authors.forename: Mie
authors.initials: M
authors.lastname: Kristensen
authors.affiliation: Department of Pharmacy, Section for Biologics, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark.
authors.forename: Hanne Mørck
authors.initials: HM
authors.lastname: Nielsen
mesh_terms: D000818:Animals; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D004848:Epithelium / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption
chemical_list: D057846:Cell-Penetrating Peptides
keywords: cell-penetrating peptides; delivery vectors; drug delivery; epithelium; mucosal barriers; non-injectable delivery; peptide and protein drugs