Biol. Pharm. Bull. 28(10) 2007—2010 (2005)

ease progressing to end-stage renal failure. Renal fibrosis is characterized by qualitative and quantitative changes in the composition of tubular basement membranes or interstitial matrices, tubular atrophy, and the accumulation of myofibroblasts. For chronic renal disease, persistent accumulation and deposition of extracelluar matrix (ECM) which lead to widespread tissue fibrosis, are observed. Renal interstitial fibrosis is considered to be the commonly converging outcome of chronic renal diseases with a wide spectrum of diverse etiologies. For renal fibrosis, severe accumulation of ECM is observed in the renal interstitial compartment. It is experimentally confirmed from several animal models of renal fibrosis that transforming growth factor-b (TGF-b), heat shock protein (HSP), and other cytokines function as the primary mediators for ECM accumulation. Therefore, it has been demonstrated that biological inhibition of TGF-b protein by use of neutralizing antibody, antisense oligonucleotide, and decorin, suppressed the accumulation of ECM in the animal models of renal fibrosis. However, there are some therapeutic limitations, for example, because protein or gene is rapidly degraded by enzyme after administration into the body. In addition, despite various approaches and techniques, there is a few trials on the in vivo targeting of plasmid DNA to renal interstitial cells, which have been highlighted as one cell source responsible for expressive ECM synthesis. For one strategy to overcome this problem, it is important to develop the technology and methodology of drug delivery system (DDS) for local delivery of the therapeutic drugs. We have explored a DDS technique necessary to therapeutic drugs for the long-term and stable expression of biologically active substance. As one DDS carrier for the local delivery of plasmid DNA, a cationized gelatin is used. The electrical nature of gelatin which can be readily changed by the processing method of collagen for preparation. An acidic processing of collagen produces “basic” gelatin with an isoelectric point (IEP) of 9.0. Based on this concept, positively charged gelatin can form a polyion complex with DNA because the nature of DNA is a macromolecule of negative charges. Complexation with the biodegradable cationized gelatin enabled some plasmid DNAs to enhance their level of gene transfection in vivo. Complexation also reduced the DNase digestion of plasmid DNA and prolonged the in vivo remaining time period of plasmid DNA. In addition, the apparent molecular size of plasmid DNA was decreased and the surface charge of plasmid DNA became positive by complexation with the cationized gelatin. It is likely that these features resulted in acceleration of in vivo gene expression. However, unfortunately, the complex of cationized gelatin does not have any inherent natures of targeting to a specific cell. Thus, as one practical possible way to overcome the notargetability, contriving the administration route will be promising. This study is a technological trial to deliver the enhanced green fluorescent protein (EGFP) plasmid DNA complexed with the cationized gelatin into renal interstitial fibroblasts which are currently considered as the cell source responsible for excessive ECM synthesis. It is well recognized that the ureteral stenosis is one of the pathogenic characteristics of renal interstitial fibrosis and responsible for the intrinsic renal pressure increase. The objective of this study is to enhance the level of gene transfection in the disease kidney with an increased renal pressure. This study experimentally shows the gene transfection of renal interstitial cells after retrograde injection of plasmid DNA complexed with cationOctober 2005 Notes Biol. Pharm. Bull. 28(10) 2007—2010 (2005) 2007