Marcilli Raphael H M, de Oliveira Marcelo G
Institute of Chemistry, University of Campinas, UNICAMP, Campinas, 13083-970, SP, Brazil.
Institute of Chemistry, University of Campinas, UNICAMP, Campinas, 13083-970, SP, Brazil.
Colloids Surf B Biointerfaces. 2014 Apr 1;116:643-51. doi: 10.1016/j.colsurfb.2013.10.036. Epub 2013 Oct 29.
Pathological conditions associated with the impairment of nitric oxide (NO) production in the vasculature, such as Raynaud's syndrome and diabetic angiopathy, have stimulated the development of new biomaterials capable of delivering NO topically. With this purpose, we modified poly(vinyl-alcohol) (PVA) by chemically crosslinking it via esterification with mercaptosuccinic acid. This reaction allowed the casting of sulfhydrylated PVA (PVA-SH) films. Differential scanning calorimetry and X-ray diffractometry showed that the crosslinking reaction completely suppressed the crystallization of PVA, leading to a non-porous film with a homogeneous distribution of -SH groups. The remaining free hydroxyl groups in the PVA-SH network conferred partial hydrophylicity to the material, which was responsible for a swelling degree of ca. 110%. The PVA-SH films were subjected to an S-nitrosation reaction of the -SH groups, yielding a PVA containing S-nitrosothiol groups (PVA-SNO). Amperometric and chemiluminescence measurements showed that the PVA-SNO films were capable of releasing NO spontaneously after immersion in physiological medium. Laser Doppler-flowmetry, used to assess the blood flow in the dermal microcirculation, showed that the topical application of hydrated PVA-SNO films on the health skin led to a dose- and time-dependent increase of more than 5-fold in the dermal baseline blood flow in less than 10min, with a prolonged action of more than 4h during continuous application. These results show that PVA-SNO films might emerge as a new material with potential for the topical treatment of microvascular skin disorders.
与血管中一氧化氮（NO）生成受损相关的病理状况，如雷诺氏综合征和糖尿病性血管病，推动了能够局部递送NO的新型生物材料的开发。为此，我们通过与巯基琥珀酸进行酯化反应对聚乙烯醇（PVA）进行化学交联改性。该反应使得能够浇铸巯基化PVA（PVA-SH）薄膜。差示扫描量热法和X射线衍射法表明，交联反应完全抑制了PVA的结晶，形成了具有均匀分布的-SH基团的无孔薄膜。PVA-SH网络中剩余的游离羟基赋予材料部分亲水性，这使得材料的溶胀度约为110%。对PVA-SH薄膜的-SH基团进行S-亚硝基化反应，得到含有S-亚硝基硫醇基团的PVA（PVA-SNO）。安培法和化学发光测量表明，PVA-SNO薄膜在浸入生理介质后能够自发释放NO。用于评估真皮微循环中血流的激光多普勒血流仪显示，在健康皮肤上局部应用水合PVA-SNO薄膜会导致真皮基线血流在不到10分钟内呈剂量和时间依赖性增加超过5倍，在持续应用期间作用时间延长超过4小时。这些结果表明，PVA-SNO薄膜可能成为一种有潜力用于局部治疗微血管性皮肤疾病的新材料。
