(419e) Hybrid Stealth Liposomes: Addition of Pendant-Cholesterol Block Copolymers to Phospholipid Vesicles

The ability of block copolymers to self-assemble in aqueous solution, resulting in nanoscale structures, makes them viable platforms for drug delivery vehicles and therapeutic agents. In this thrust, a number of recent efforts have focused on chemically incorporating bio-inspired functionalities including cholesterol into the hydrophobic block of amphiphilic block copolymers. The molecular shape and intermolecular interactions (e.g. pi-pi stacking) in these materials can lead to intriguing structures such as disk and stacked-disk shaped micelles. Here, we extend the versatility of one such molecule, poly[(ethylene glycol)-b-(2-(5-methyl-2-oxo-1,3-dioxane-5-carboxyloyloxy)ethyl carbamate)] (PEG-P(MTC-Chol)), by combining a minority quantity with phospholipids capable of forming vesicles (also called liposomes). The P(MTC-Chol) blockâ??s pendant cholesterol groups can collocate in the phospholipid bilayer, much like unbound cholesterol. The PEG block, on the other hand, prefers to extend itself into aqueous solution. A valid hypothesis might, therefore, be that the block copolymer chains will tether to the liposome bilayer through cholesterol insertion with the extended PEG sterically stabilizing the otherwise unstable liposome assemblies (as in stealth liposomes). In practice, this hypothesis remains true only if the number of cholesterol groups per chain is low. The block copolymer may prefer to form separate micelles or extract from liposomes as the P(MTC-Chol) block becomes too long, leaving the liposomes unmodified. In this work, the critical P(MTC-Chol) block length dividing the two cases was identified primarily through dynamic light scattering. Successfully formed hybrid stealth liposomes are further investigated in terms of their bilayer nanostructure and thermodynamics through a combination of cryo-electron microscopy, small angle scattering, and calorimetry.