ABSTRACT

Efforts to create effective DNA-based therapeutics have been hampered by well-known factors, including the body’s defense system, which serves to inactivate them. Poly(lactide-co-glycolide) (PLG)-based delivery systems have inherent characteristics that offer promise in this field of research. This chapter will focus on information related to DNA expression vectors formulated

with PLG microparticles. These formulations can protect DNA from nuclease-based attack, facilitate DNA localization to cells and tissues of interest, and promote gene expression; furthermore, they have the potential to provide for controlled release. Safety and the application of PLG formulations to clinical medicine have been proven by the commercial success of PLG depot systems that allow for slow release of peptides (LHRH agonists, Lupron Depot®, Zoladex®) and proteins (human growth hormone, Nutropin Depot®). The following sections provide an overview of key characteristics of PLG-DNA formulations, processes for their manufacture, and their biological activity.