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 β-cyclodextrin (β-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.