Three-armed biodegradable star polymers made from polystyrene (polySt) and poly (polyethylene glycol) acrylate (polyPEG-A) were synthesized via a core first methodology using a trifunctional RAFT agent, created by attaching RAFT agents to a core via their R-groups. The resultant three-armed polymeric structures were well-defined, with polydispersity indices less than 1.2. Upon aminolysis and further reaction with dithiodipyridine (DTDP), these three-armed polymers could be tailored with sulfhydryl and pyridyldisulfide (PDS) end functionalities, available for further reaction with any free-sulfhydryl group containing precursors to form disulfide linkages. Nuclear magnetic resonance (NMR) confirmed that more than 98 of the polymer arms retained integral trithiocarbonate active sites after polymerization. Intradisulfide linkages between the core and the arms conferred biodegradability on the star architectures. Subsequently, the arm-termini were attached to cholesterol also via disulfide linkages. The cholesterol terminated arms were then used to form supramolecular structures via inclusion complex formation with ?-cyclodextrin (?-CD). The star architectures were found to degrade rapidly on treatment with DL-dithiothereitol (DTT). The star polymers and supramolecular structures were characterized using gel permation chromatography (GPC), static light scattering (SLS), 2D NMR, and fluorescence spectroscopy.