S-nitrosothiol-terminated poly(vinyl alcohol): Nitric oxide release and skin blood flow response

Leonardo P Giglio; Guilherme F Picheth; Kaja Borup Løvschall; Alexander N Zelikin; Marcelo G de Oliveira

doi:10.1016/j.niox.2020.03.002

S-nitrosothiol-terminated poly(vinyl alcohol): Nitric oxide release and skin blood flow response

Nitric Oxide. 2020 May 1:98:41-49. doi: 10.1016/j.niox.2020.03.002. Epub 2020 Mar 6.

Authors

Leonardo P Giglio¹, Guilherme F Picheth¹, Kaja Borup Løvschall², Alexander N Zelikin³, Marcelo G de Oliveira⁴

Affiliations

¹ Institute of Chemistry, University of Campinas, Unicamp, 13083-861, Campinas, SP, Brazil.
² Department of Chemistry, Aarhus University, Aarhus, C 8000, Denmark.
³ Department of Chemistry, Aarhus University, Aarhus, C 8000, Denmark; INano Interdisciplinary Nanoscience Center, Aarhus University, Aarhus, C 8000, Denmark.
⁴ Institute of Chemistry, University of Campinas, Unicamp, 13083-861, Campinas, SP, Brazil. Electronic address: mgo@unicamp.br.

PMID: 32147583
DOI: 10.1016/j.niox.2020.03.002

Abstract

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-NH₂), 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^-1 min^-1, 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.

Keywords: Nitric; Oxide; Poly(vinyl alcohol); Reversible addition-fragmentation chain transfer (RAFT); S-nitrosothiol; Skin blood flow.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Blood Flow Velocity
Humans
Nitric Oxide / metabolism*
Polyvinyl Alcohol / metabolism*
S-Nitrosoglutathione / metabolism*
Skin / blood supply
Skin / metabolism*

Substances

Nitric Oxide
S-Nitrosoglutathione
Polyvinyl Alcohol