Rationally Designing Peptide Amphiphile Micelles for Use As Targeted Drug Delivery Vehicles

Peptide amphiphile micelles provide a modular design platform for the creation of targeted drug delivery vehicles.  Peptide amphiphiles are formed by conjugating a hydrophilic peptide headgroup to a hydrophobic lipid tail.  The peptides used in the formation of these peptide amphiphiles are designed to target specific sites of interest in the body.  Our approach is to use two peptides that can target both early stage inflammation markers of atherosclerosis as well as late stage markers of atherosclerotic plaques.  Atherosclerosis, characterized by the formation of a plaque in the artery wall, can lead to heart disease, the leading cause of death in the United States.  The formation of a targeted vehicle that can selectively deliver a therapeutic agent at the site of plaque formation is thus highly desirable as such targeted therapeutics are not currently available.  In order to develop such a therapeutic delivery agent, however, it is first necessary to determine how the specific components of the peptide amphiphile micelle, namely the hydrophilic head group and hydrophobic tail, affect the size, shape, and stability of the micelle formed.  We will thus discuss how changing the peptide targeting agent and the hydrophobic tail affect the dissociation kinetics of the micelle and how we can increase the micelle’s half life in vitro.  In addition, we will present both dynamic light scattering (DLS) data and transmission electron microscopy (TEM) images to show the size and shape micelles that are formed.  Both spherical micelles with a diameter on the order of 10-20 nm and cylindrical micelles will be discussed.  The critical micelle concentration (CMC), or the concentration at which micelles begin to form, provides insight into the stability of micelles.  The ability to tailor the CMC based upon the hydrophobic tail will also be discussed.  Enzymes play an important role in degrading peptides in vivo, and we will thus discuss how the formation of micelles affects the degradation of peptides in the corona as compared to a peptide control.  Finally, we will show the in vitro binding capabilities of micelles formed from these early and late stage targeting peptides.