Novel delivery of oligonucleotides using a topical hydrogel tissue sealant in a murine partial nephrectomy model.

ABSTRACTPurpose: Ischemia/reperfusion injury is a leading cause of renal damage and antisense gene therapy has been shown to ameliorate its effects. However, this approach has been limited by current delivery methods that require high concentrations of intravenous nucleic acids lacking specificity for targeting tissues. To overcome these limitations we developed a novel murine partial nephrectomy model to evaluate polyethylene-glycol (PEG) hydrogel tissue sealant as a topical oligonucleotide delivery system.Materials and Methods: A total of 18 male C57BL/6 mice underwent left partial nephrectomy with vascular occlusion. Hydrogel primer and then sealant were applied to the cut surface and photopolymerized. Using this method 16 additional mice received hydrogel primer mixed with Cy5 labeled fluorescent oligonucleotide (10 to 100 μg). Kidneys were harvested at various time points and assessed for oligonucleotide penetration using fluorescence microscopy.Results: A survival rate of 100% (34 subjects) was obta...