title: Bioactive self-assembling lipid-like peptides as permeation enhancers for oral drug delivery.
abstract: Amphiphilic, lipid-like, self-assembling peptides are functional biomaterials with surfactant properties. In this work, lipid-like peptides were designed to have a hydrophilic head composed of aspartic acid or lysine and a six alanine residue hydrophobic domain and have a length similar to that of biological lipids. The aim of this work was to examine the potential of using ac-A6 K-CONH2 , KA6 -CONH2 , ac-A6 D-COOH, and DA6 -COOH lipid-like peptides as permeability enhancers to facilitate transport through the intestinal barrier. In vitro transport studies of the macromolecular fluorescent marker fluorescein isothiocyanate (FITC)-dextran (4.4 kDa) through Caco-2 cell monolayers show the permeation enhancement ability of the lipid-like peptides. We observed increased FITC-dextran transport across the epithelial monolayer up to 7.6-fold in the presence of lipid-like peptides. Furthermore, we monitored the transepithelial resistance and performed immunofluorescence studies of the cell tight junctions. Ex vivo studies showed increased mucosal to serosal absorption of FITC-dextran in rat jejunum in the presence of the ac-A6 D-COOH peptide. Furthermore, a small increase in the serosal transport of bovine serum albumin was observed upon addition of ac-A6 D-COOH. Lipid-like peptides are biocompatible and they do not affect epithelial cell viability and epithelial monolayer integrity. Our results suggest that short, lipid-like peptides may be used as permeation enhancers to facilitate oral delivery of diagnostic and therapeutic molecules.
authors.affiliation: School of Pharmacy, Aristotle University of Thessaloniki, Department of Pharmaceutical Technology, Thessaloniki, GR-54124, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Karavasili
authors.affiliation: School of Pharmacy, Aristotle University of Thessaloniki, Department of Pharmacology and Molecular Biology, Thessaloniki, GR-54124, Greece.
authors.forename: Marios
authors.initials: M
authors.lastname: Spanakis
authors.affiliation: School of Pharmacy, Aristotle University of Thessaloniki, Department of Pharmaceutical Chemistry, Thessaloniki, GR-54124, Greece.
authors.forename: Dionysia
authors.initials: D
authors.lastname: Papagiannopoulou
authors.affiliation: School of Pharmacy, Aristotle University of Thessaloniki, Department of Pharmacology and Molecular Biology, Thessaloniki, GR-54124, Greece.
authors.forename: Ioannis S
authors.initials: IS
authors.lastname: Vizirianakis
authors.affiliation: School of Pharmacy, Aristotle University of Thessaloniki, Department of Pharmaceutical Technology, Thessaloniki, GR-54124, Greece.
authors.forename: Dimitrios G
authors.initials: DG
authors.lastname: Fatouros
authors.affiliation: Center for Biomedical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139.
authors.forename: Sotirios
authors.initials: S
authors.lastname: Koutsopoulos
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D018938:Caco-2 Cells; D003911:Dextrans / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D004847:Epithelial Cells / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007408:Intestinal Absorption / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism; D008055:Lipids / Q000008:administration & dosage*; D010455:Peptides / Q000008:administration & dosage* / Q000378:metabolism*; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D019108:Tight Junctions / Q000378:metabolism
chemical_list: D003911:Dextrans; D008055:Lipids; D010455:Peptides; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate
keywords: Caco-2 cells; absorption enhancer; designed tunable peptides; epithelial delivery; everted sacs; formulation; intestinal absorption; lipid-like peptides; macromolecular drug delivery; oral absorption; surfactant