Institute of Chemistry, University of Campinas, Unicamp, 13083-861, Campinas, SP, Brazil.
Department of Chemistry, Aarhus University, Aarhus, C 8000, Denmark.
Nitric Oxide. 2020 May 1;98:41-49. doi: 10.1016/j.niox.2020.03.002. Epub 2020 Mar 6.
Polymeric biomaterials capable of delivering nitric oxide (NO) topically can be used to enhance skin blood flow (SkBF) and accelerate wound healing. Herein, we used reversible addition-fragmentation chain transfer radical (RAFT) polymerization to synthesize the first poly(vinyl alcohol) (PVA) functionalized with terminal NO-releasing S-nitrosothiol (RSNO) groups for topical NO delivery. This strategy was based on the synthesis of a precursor amino-terminated PVA (PVA-NH), which was next functionalized with iminothiolane yielding 4-imino-4-amino-PVA-butane-1-thiol (PVA-SH), and finally S-nitrosated yielding S-nitroso 4-imino-4-amino-PVA-butane-1-thiol (PVA-SNO). Real-time chemiluminescence NO detection showed that blended films of pure PVA with PVA-SNO with mass ratios 30:70, 50:50 and 70:30 release NO with initial rates ranging from 1 to 12 nmol g min, and lead to a 2 to 10-fold dose-response increase in the SkBF, after topical application on the ventral forearm of volunteers. These results show that PVA-SNO is a potential platform for topical NO delivery in biomedical applications.
能够局部递送一氧化氮 (NO) 的聚合生物材料可用于增强皮肤血流量 (SkBF) 和加速伤口愈合。在此，我们使用可逆加成-断裂链转移自由基聚合 (RAFT) 聚合来合成第一种带有末端 NO 释放 S-亚硝基硫醇 (RSNO) 基团的聚(乙烯醇) (PVA)，用于局部 NO 递送。该策略基于合成末端氨基封端的 PVA（PVA-NH）的合成，其随后与亚氨酸硫醇反应得到 4-亚氨基-4-氨基-PVA-丁烷-1-硫醇（PVA-SH），最后 S-亚硝化得到 S-亚硝基 4-亚氨基-4-氨基-PVA-丁烷-1-硫醇（PVA-SNO）。实时化学发光 NO 检测表明，纯 PVA 与 PVA-SNO 的混合膜以质量比 30:70、50:50 和 70:30 释放 NO 的初始速率范围为 1 至 12 nmol g min，并且导致志愿者腹侧前臂局部应用后 SkBF 增加 2 至 10 倍。这些结果表明 PVA-SNO 是生物医学应用中局部 NO 递送的潜在平台。
