Lipid-like Self-Assembling Peptide Nanovesicles for Drug Delivery

[Image: see text] Amphiphilic self-assembling peptides are functional materials, which, depending on the amino acid sequence, the peptide length, and the physicochemical conditions, form a variety of nanostructures including nanovesicles, nanotubes, and nanovalves. We designed lipid-like peptides with an aspartic acid or lysine hydrophilic head and a hydrophobic tail composed of six alanines (i.e., ac-A(6)K-CONH(2), KA(6)-CONH(2), ac-A(6)D-COOH, and DA(6)-COOH). The resulting novel peptides have a length similar to biological lipids and form nanovesicles at physiological conditions. AFM microscopy and light scattering analyses of the positively charged lipid-like ac-A(6)K-CONH(2), KA(6)-CONH(2) peptide formulations showed individual nanovesicles. The negatively charged ac-A(6)D-COOH and DA(6)-COOH peptides self-assembled into nanovesicles that formed clusters that upon drying were organized into necklace-like formations of nanovesicles. Encapsulation of probe molecules and release studies through the peptide bilayer suggest that peptide nanovesicles may be good candidates for sustained release of pharmaceutically active hydrophilic and hydrophobic compounds. Lipid-like peptide nanovesicles represent a paradigm shifting system that may complement liposomes for the delivery of diagnostic and therapeutic agents.