Understanding electrostatics in polymersomes, monolayers, and worm-like micelles with application to NIR imaging and tumor-bearing mice

Amphiphilic molecules, specifically lipids and amphiphilic diblock copolymers, are well known to self-assemble to form micelles of varying architecture. The ability to tune the physical properties of these assemblies by varying the properties of the amphiphile have been well elucidated. In contrast, how the electrostatic interaction between the amphiphile and soluble factors affects the morphology, physical properties, or lateral heterogeneity of these assemblies is not well understood but equally important. This thesis aims to better elucidate how electrostatic interactions affect the structure of both polymeric and lipid assemblies, and apply this understanding to determine how micellar charge and morphology affect the properties of drug delivery vehicles in vivo.;The primary focus of this thesis is to study the effect of electrostatic interactions between polyanionic amphiphiles and multivalent cations. The divalent cation calcium is shown to have dramatic affects on the lateral organization of diblock copolymer vesicles (polymersomes) and worm-like micelles composed of blends of a neutral diblock copolymer and a polyanionic diblock copolymer. Interactions between calcium and the polyanionic block were shown to have strong effects on the rigidity and fluidity of polymersomes. In blended systems, a small range of calcium concentrations and pH induce laterally segregated domains in polymersomes and worm-like micelles.;To determine whether these effects were exclusive to calcium or polymeric amphiphiles, the studies were expanded to include other multivalent cations with the polymer system and calcium with a polyanionic lipid in blended lipid monolayers. By varying the type of multivalent cation, blended polymersomes display phase separated domains of varying shape and size. The lipid model system also displayed electrostatic-induced architectural changes in the monolayer upon the addition of calcium.;This work with charged amphiphiles was expanded to better elucidate the roles surface charge and micellar shape play in biodistribution and therefore drug delivery. By loading polymeric micelles with a NIR fluorophore, these effects could be efficiently analyzed. These labeling techniques allowed for the study of how shape affects drug delivery to solid tumors. Finally, to develop these carriers toward a therapeutic use, neutral polymersomes were used to encapsulate a model therapeutic protein - insulin.