Treatment of blood flow abnormality using mucosal delivery of nitric oxide.

This review focuses on clinical application of intravaginal formulations containing nitric oxide (NO). Poly(D,L-lactic acid-co-glycolic acid)-based microparticles or nanoparticles encapsulated with nitric oxide prodrugs, such as diethylenetriamine diazeniumdiolate and S-nitrosoglutathione, have been developed for the treatment of blood flow abnormality in various diseases including diabetes. Advanced nanotechnology allows for production of novel formulations with the capability of long-term protection, preserving the integrity of the NO donors, and delivering NO in a controlled and sustained release manner at the mucosal sites. The gene expressions of MAPK and PKC in the vaginal mucosa upon exposure to microparticles were evaluated for the mechanistic study involved with blood flow changes. The blood flow changes and protein expression of the vaginal mucosa upon exposure to intravaginal formulations containing NO donors supported that NO therapy would be suitable for the treatment of blood flow abnormality. This review subsequently would help to establish a scientific foundation for clinical trials of intravaginal NO delivery systems in humans.