RNA interference (RNAi) is the process where the introduction of double stranded RNA into a cell inhibits gene expression in a sequence dependent fashion. However, advanced drug delivery, systemic distribution and long-term silencing of genes are necessary before gene therapy can enter the clinical phase and eventually benefit patients. It is essential that the drug carrier system be capable of delivering siRNA therapeutics to the target cells. One emerging and promising technique is to use biodegradable polymeric nanoparticle drug delivery systems. The goals of this project are to prepare, characterize and optimize nanoparticle carrier systems to deliver siRNA by a cationic PEI complex. The siRNA drug delivery is a new, exciting and yet very challenging area in pharmaceutical research. The long-term objective is to achieve enhanced and targeted delivery of siRNA to cells using the proposed nanoparticle carrier system. The siRNA/PEI complex will be prepared and loaded into biodegradable PLGA nanoparticle delivery system, which will be characterized in terms of particle size, size distribution and surface morphology using quasi-elastic laser scattering particle sizer and scanning electron microscopy (SEM). The drug loading efficiency, drug stability and in vitro evaluation of the new nanoparticle delivery system will be studied using UV, HPLC, RNase protection assay and dissolution testing. Transfection and gene silencing studies of ds-GFP-siRNA loaded nanoparticle drug delivery system will be done in cell culture using 293T cell line. At the protein level, the green fluorescent intensity of GFP will be monitored through fluorescent microscopy.