DESCRIPTION (provided by applicant): Single molecule spectroscopic techniques will be used to assay the physical properties of controlled drug delivery systems, unimolecular amphiphilic nanocarriers (UAN). We will relate the physical properties of the UAN's polymer core to its ability to solubilize and deliver drug molecules. The specific aims of this project are to understand the encapsulation process that protects and solubilizes the drug molecule, and to determine the process of distribution and delivery of the drug molecule; a UAN can be used not only to solubilize a hydrophobic drug molecule, but also to protect it from environmental degradation. These studies will also help determine what factors will enable the UAN to better deliver the drug through cell membranes. The principle techniques in studying encapsulation, will be environmentally sensitive bulk and single molecule time resolved spectroscopy. A series of UAN's with modified polymer cores will be used to determine how the different flexibilities of the polymer effect solubilization of a fluorescent probe molecule. To assess the ability of a UAN to preferentially deliver drugs by permeating a membrane, actual delivery of bioactive molecules to liposomes will be dynamically imaged using scanning confocal microscopy and single molecule detection.