The objective of this proposal is to evaluate the potential of using polymeric carriers for drug delivery to the central nervous system through intracranial implantation. The delivery systems will be designed from the biodegradable polyanhydrides and the novel poly(phosphate esters). An injectable delivery system will also be conceived of the poly(phosphate ester) through microencapsulation formulation. Through the use of model compounds and representative therapeutic drugs, we hope to identify-- through theory and supporting experimentation--the promise and limitations of this mode of localized and sustained drug delivery for neurological applications. The diffusion and clearance characteristics of sucrose, dextrans, aminoiodopyridien, 5-fluorouracil, and nerve growth factor delivered by different formulations into the rabbit brain will be studied using quantitative autoradiography. Direct injection of selective drugs into the brain tissue will be used as the reference. Based on the quantitative autoradiographic data, mathematical models will be constructed to quantify the transport of the drugs in the brain. Attempts will be made to relate the physiochemical properties and the in vitro release profile of the drugs intensity, distribution, duration, and possible local toxicity in the brain. It is hoped that these studies will provide a solid and rational foundation for the application of this new technology to CNS disorders.
| Reisfeld, B; Blackband, S; Calhoun, V et al. (1993) The use of magnetic resonance imaging to track controlled drug release and transport in the brain. Magn Reson Imaging 11:247-52 |
| Dang, W; Saltzman, W M (1992) Dextran retention in the rat brain following release from a polymer implant. Biotechnol Prog 8:527-32 |
