Evaluation of linear polyethyleneimine/nitric oxide adduct on wound repair: therapy versus toxicity.

A full-thickness wound model was used to evaluate the effects of a topically applied polyethyleneimine-based nitric oxide donor on wound repair in aged rats. Polymer applications were applied over a 10-day period on days 0, 2, 4, 6, and 8 comparing treatment (linear polyethyleneimine-nitric oxide) and control groups (linear polyethyleneimine). Urinary nitrate excretion was quantified as a measure of nitric oxide released. The nitric oxide released from the linear polyethyleneimine-nitric oxide group was significant compared with controls (p </= 0.001), with a maximal nitrate level of 40 micromol on day 1 and an average sustained delivery of 34 micromol/day for the remainder of the study. Wound closure was examined using a computer-based video-imaging analysis system. The wounds of both the linear polyethyleneimine- nitric oxide treatment and linear polyethyleneimine control groups exhibited minimal wound closure; however, the wound closure of the treatment group was significant as compared with the control group (p </= 0.05). A phosphate- buffered saline solution-wounded control was performed that showed cleaner and faster healing wounds, similar to normal healing, than either of the polymer application groups. The histological data showed very little wound healing, on a cellular level, implicating the linear polyethyleneimine-nitric oxide as well as the carrier compound as contributing to the adverse tissue reactions that occurred in the wound bed. Thus, we report the toxic effects of a polyethyleneimine-based compound, as well as the toxic effects of sustained delivery of excess levels of nitric oxide on the wound- repair process. Our findings suggest that there exists indeterminate parameters between therapy and toxicity of nitric oxide delivery to wounds.