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-A 6 K-CONH 2 , KA 6 -CONH 2 , ac-A 6 D-COOH, and DA 6 -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-A 6 D-COOH peptide. Furthermore, a small increase in the serosal transport of bovine serum albumin was observed upon addition of ac-A 6 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.