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热和光化学诱导的一氧化氮从掺入普朗尼克F127凝胶中的S-亚硝基硫醇释放:一氧化氮局部和可控释放的潜在用途。

Thermal and photochemical nitric oxide release from S-nitrosothiols incorporated in Pluronic F127 gel: potential uses for local and controlled nitric oxide release.

作者信息

Shishido Sílvia Mika, Seabra Amedea Barozzi, Loh Watson, Ganzarolli de Oliveira Marcelo

机构信息

Instituto de Química, Universidade Estadual de Campinas (UNICAMP), CP 6154, Campinas, SP 13083-970, Brazil.

出版信息

Biomaterials. 2003 Sep;24(20):3543-53. doi: 10.1016/s0142-9612(03)00153-4.

Abstract

The local delivery of nitric oxide (nitrogen monoxide, NO) by thermal or photochemical means to target cells or organs has a great potential in several biomedical applications, especially if the NO donors are incorporated into non-toxic viscous matrices. In this work, we have shown that the NO donors S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylcysteine (SNAC) can be incorporated into F127 hydrogels, from where NO can be released thermally or photochemically (with lambda(irr)>480nm). High sensitivity differential scanning calorimetry (HSDSC) and a new spectrophotometric method, were used to characterize the micellization and the reversal thermal gelation processes of the F127 hydrogels containing NO donors, and to modulate the gelation temperatures to the range 29-32 degrees C. Spectral monitoring of the S-NO bond cleavage showed that the initial rates of thermal and photochemical NO release (ranging from 2 to 45 micromoll(-1)min(-1)) are decreased in the hydrogel matrices, relative to those obtained in aqueous solutions. This stabilization effect was assigned to a cage recombination mechanism and offers an additional advantage for the storage and handling of S-nitrosothiols. These results indicate that F127 hydrogels might be used for the thermal and photochemical delivery of NO from S-nitrosothiols to target areas in biomedical applications.

摘要

通过热或光化学手段将一氧化氮(NO)局部递送至靶细胞或器官在多种生物医学应用中具有巨大潜力,尤其是当NO供体被掺入无毒粘性基质中时。在这项工作中,我们已经表明,NO供体S-亚硝基谷胱甘肽(GSNO)和S-亚硝基-N-乙酰半胱氨酸(SNAC)可以掺入F127水凝胶中,从那里NO可以通过热或光化学方式释放(λ(irr)>480nm)。使用高灵敏度差示扫描量热法(HSDSC)和一种新的分光光度法来表征含有NO供体的F127水凝胶的胶束化和逆转热凝胶化过程,并将凝胶化温度调节至29-32摄氏度范围。对S-NO键断裂的光谱监测表明,相对于在水溶液中获得的初始速率,水凝胶基质中热和光化学NO释放的初始速率(范围为2至45μmol·l(-1)·min(-1))降低。这种稳定化效应归因于笼状重组机制,并为亚硝基硫醇的储存和处理提供了额外的优势。这些结果表明,F127水凝胶可用于在生物医学应用中将亚硝基硫醇中的NO热和光化学递送至靶区域。

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