Biodegradable Microparticles for in vivo Glomerular Targeting: Implications for Gene Therapy of Glomerular Disease

Abstract

Glomerular disease is the most common cause of kidney failure in the United States. Gene therapy represents a novel approach to the treatment of diseases of the glomerulus, but necessitates safe and accurate tissue targeting, combined with efficient gene transfer into the cells of interest. Our previous work demonstrated effective glomerular gene transfer after arterial injection of replication deficient recombinant adenovirus complexed to 16 μm polystyrene microspheres. The insoluble nature of polystyrene makes glomerular ischemia a potential complication of the procedure. On this basis, we postulated that biodegradable gelatin particles could serve as transport vehicles in this system. To address this question, we assessed the in vivo degradation of Tc-99m labeled gelatin or polystyrene particles in the kidney following selective renal artery injection. Radioactivity declined 2–3 fold faster in a gelatin-injected pig kidney, when compared to polystyrene injected animals. The discrepancy in signal loss between gelatin and polystyrene injected animals could not be explained by differences in the rate of dissociation of Tc-99m from each particle type, and suggest that gelatin particles degrade once lodged in the glomerular capillary. These data suggest that biodegradable gelatin particles may help to minimize ischemic potential when used to shuttle therapeutic DNA to the glomerulus.