The medicinal benefits of the nitric oxide (NO) donor compounds termed diazeniumdiolates are well established and include antithrombic, cytostatic, and vasorelaxant activities. Additionally, fendiline, a coronary vasodilator, increases intracellular NO concentrations via interaction with the calcium cascade. Modification of fendiline with NO generates a new, lipophilic member of the diazeniumdiolate family, fendiline diazeniumdiolate (FDL-NONa), which has increased potential as a pharmaceutical NO donor and multiple applications in the coronary health market. This bifunctional vasodilator, when dissolved in methanol and buffer solution, releases NO to generate a half-life of 1.6 hours at 37°C and pH 7.4. Extension of this half-life can be achieved by varying the water insoluble particulate size of the donor in PBS. Furthermore, excellent binding of FDL-NONa to both glass and metal surfaces provides a direct correlation between coating thickness and NO release profile while decomposition of the compound in vivo generates species which pose no health concern.
In additional to numerous functions within the cardiovascular system, NO has also been established as an indispensable participant in the wound healing cascade. Based on these findings, multiple NO-based wound dressings have been developed for employment in impaired wound healing scenarios. One example is the ascorbic acid/nitrite patch, which has displayed very promising results in both diabetic and lechmaniasis wounds, however has several drawbacks including donor half-life, patch stability and product manufacturing costs. To correct these problems, a new two-layer, PAN-NO (polyacrylonitrile modified with nitric oxide) pouch has been developed. Modification of previously electrospun PAN nanofibers results in the formation of a new polymeric PAN-NO patch that provides a 30 min increase in patch half-life, with extension of the total release time by 4 to 5 h and a nearly 17x increase in NO release from the four-layer, ascorbic acid/nitrite patch when modified in sodium trimethylsilanolate/1,4-dioxane or a 4 h increase in patch half-life, with an extension of the total release time by 27 to 28 h and a comparable NO/mg release when modified in sodium methoxide. Insertion of either form of PAN-NO into a heat-sealed, ascorbic acid pouch forms a second generation, NO-donating wound dressing, with reduced manufacturing costs and improved NO release kinetics.