Abstract
This chapter discusses sustained intracerebral delivery of nerve growth factor (NGF) with biodegradable polymer microspheres. Prolonged administration of NGF has been demonstrated to have a therapeutic action in several models of degenerative neurological diseases, including Alzheimer's disease (AD), and in augmenting the survival of adrenal medullary grafts in Parkinson's disease (PD). Penetration of the blood–brain barrier (BBB) by these protein growth factors is limited in their naturally occurring state. To increase intracerebral distribution, local drug delivery strategies have been developed, including local infusion with mechanical and osmotic pumps and local synthesis and delivery by genetically modified cells and NGF-producing tumor cells. Another approach has been the use of biocompatible, biodegradable polymers. The chapter describes the methodology for encapsulation of NGF in poly(l-lactide)coglycolide microspheres, using a modified triplephase solvent evaporation technique. It discusses in vitro and in vivo evaluation of NGF release from this polymer. The chapter explains the effects of NGF delivered from polymer microspheres on the functional outcome of adrenal medullary grafts in parkinsonian rodents.
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