(686e) Amphiphilic Polypeptoids and Their Hydrophobic Interactions with Lipid Bilayers - Fundamentals and Translation to Drug Delivery Systems

Hydrophobically modified polypeptoids (HMPs) are amphiphilic pseudo-peptidic macromolecules with hydrophobic groups attached randomly along the polypeptoid backbone. We show that these biocompatible polymers connect across lipid bilayers and thus form layered structures on liposomes. The transition from single bilayer to multiple bilayer structures is characterized by small angle neutron scattering (SANS) and cryo-transmission electron microscopy (cryo-TEM). We propose a mechanism whereby the HMPs insert their hydrophobic side chains into adjacent bilayers and thereby serve as the connective glue between bilayers. At higher HMP concentrations, the liposomes are entirely disrupted into much smaller micelle-like structures through extensive hydrophobe insertion. Interestingly, these small structures can reattach to fresh unilamellar liposomes and self-assemble to form new two-bilayered liposomes reminiscent of two-bilayered organelles such as the nucleus in eukaryotic cells. The observations have significance to designing new nanoscale drug delivery carriers.