Although drugs, especially peptides and proteins, are now available to provide new therapies for neurological diseases, the use of the drugs as therapeutic agents is still hampered by the lack of an effective route and method of delivery. This is due to the fact that many of the drugs do not cross the blood-brain barrier (BBB), have short half-life, are easily metabolized when administered peripherally and possess biological activity at multiple tissue sites throughout the body. In view of these difficulties, we are interested in developing controlled drug delivery systems to release one or several type drugs cross the BBB to the aimed direction and organ at the corresponding amount and at the fixed time. Biodegradable polymers play an important role in drug delivery, and have been used to circumvent the restrictions imposed by the blood-brain barrier, protect the released drug from the body's metabolism and clearance mechanisms, and target the drug to specific organelles, cells and sites within the body. However, biodegradable polymers used for drug delivery have problems in fabrication, irreproducible drug release kinetics, and non-responsibility to physiological changes in a living body. To overcome these problems, we design and synthesize a new class of biopolymers with both biodegradable and responsive characteristics for providing precisely controlled and sustained drug delivery. We control the biopolymers' biodegradability and response to physical, chemical or biological stimuli (such as temperature, pH, and ionic strength et al.) and drugs' permeability across the BBB by modifying their chemical structures with hydrophobic and hydrophilic units and electric charges. In our further strategies to tailor the biopolymers with desired physicochemical properties, we synthesize the biopolymers in the forms of multi core/shell copolymers, nano(micro)gels, macroscopic hydrogels and dendrimers. By using sophisticated physicochemical experimental techniques, we investigate the physical basis of how the structure and properties of these biopolymers derive from their molecular scale architecture and the manner in which the molecules respond to chemical or physical stimuli. By using principles and techniques of engineering, biophysics and biology, we quantitatively characterize the mechanisms by which the polymeric delivery devices regulate predictable and reproducible release of the drugs across the BBB at the molecular level for extended durations via biodegradation and thermally controlled swelling. Finally, we evaluate the toxicity of the biopolymers and the released drugs by using in vitro and in vivo assays. Completion of this research will impact clinically effective therapies for the treatment of Alzheimer's disease and other neurological disorders.