Seabra Amedea Barozzi, de Souza Gabriela Freitas Pereira, da Rocha Lilian Lúcia, Eberlin Marcos Nogueira, de Oliveira Marcelo Ganzarolli
Departamento de Físico-Química, Instituto de Química, Universidade Estadual de Campinas, UNICAMP, Campinas, SP, Brazil.
Nitric Oxide. 2004 Nov;11(3):263-72. doi: 10.1016/j.niox.2004.09.005.
Incorporation of nitric oxide (NO) donors in non-toxic polymeric matrices can be a useful strategy for allowing topical NO delivery. We have incorporated the NO-donor S-nitrosoglutathione (GSNO) into a liquid poly(ethylene glycol) (PEG)/H2O matrix through the S-nitrosation of GSH by a NO/O2 gas mixture. Kinetic measurements of GSNO decomposition associated with NO release were performed at 25, 35, and 45 degrees C in the dark and under irradiation with UV/Vis light, lambda>480 nm and lambda=333 nm. NO release from the liquid matrix to the gas phase was confirmed by mass spectrometry. The PEG/H2O matrix stabilizes GSNO leading to expressive reductions in the initial rates of thermal and photochemical NO release, compared to aqueous GSNO solution. This matrix effect is assigned to diffusional constrains imposed on the escape of the NO and GS radicals formed in the solvent cage. This effect allows the storage of PEG-GSNO formulations for extended periods (more than 65 days at freezer) with negligible decomposition. PEG-GSNO formulation seems therefore to be applicable in topical NO delivery and GSNO displays potential as a percutaneous absorption enhancer. Moreover, the rate of NO release can be locally increased by irradiation with visible light.
将一氧化氮（NO）供体掺入无毒聚合物基质中可能是实现局部递送NO的一种有用策略。我们通过用NO/O₂气体混合物对谷胱甘肽（GSH）进行S-亚硝化，将NO供体S-亚硝基谷胱甘肽（GSNO）掺入液态聚乙二醇（PEG）/H₂O基质中。在25、35和45摄氏度下，于黑暗中以及在波长>480 nm和波长=333 nm的紫外/可见光照射下，对与NO释放相关的GSNO分解进行了动力学测量。通过质谱法确认了NO从液态基质释放到气相中。与GSNO水溶液相比，PEG/H₂O基质使GSNO稳定，导致热和光化学NO释放的初始速率显著降低。这种基质效应归因于对溶剂笼中形成的NO和GS自由基逸出所施加的扩散限制。这种效应使得PEG-GSNO制剂能够长时间储存（在冷冻条件下超过65天），分解可忽略不计。因此，PEG-GSNO制剂似乎适用于局部递送NO，并且GSNO作为经皮吸收促进剂具有潜力。此外，通过可见光照射可以局部提高NO的释放速率。
