We have studied the conformational changes of two novel amphiphilic homopolymers in water and toluene relevant to delivery applications using molecular dynamics simulations supplemented with enhanced sampling techniques. The individual homopolymer repeating units are amphiphilic with a hydrophobic dodecyl chain and a hydrophilic tetra(ethylene glycol) chain attached via ether linkages to each repeating unit of the polymer backbone. Two polymer topologies were examined: one cyclic and one an exact linear analog. Here we show that these polymers exhibit highly dynamic conformations with the side arm orientations driven by the solvent polarity. In water these polymers exhibit a compact conformation with the hydrophobic arms retracted toward the backbone core, whereas in toluene the hydrophobic arms extended into the solvent. Different from the hydrophobic arms, the hydrophilic ethylene glycol chain orientations and backbone conformations are largely unperturbed by the solvent polarity. Probing the polymer microenvironment in different solvents to examine solute uptake supports the hypothesis that these polymers can selectively encapsulate/release guest molecules depending on the solvent polarity, highlighting the potential of these polymers as drug delivery vehicles.