S-nitrosothiol-terminated Pluronic F127: Influence of microstructure on nitric oxide release

Guilherme F Picheth; Laura C E da Silva; Leonardo P Giglio; Tomás S Plivelic; Marcelo G de Oliveira

doi:10.1016/j.jcis.2020.05.049

S-nitrosothiol-terminated Pluronic F127: Influence of microstructure on nitric oxide release

J Colloid Interface Sci. 2020 Sep 15:576:457-467. doi: 10.1016/j.jcis.2020.05.049. Epub 2020 May 19.

Authors

Guilherme F Picheth¹, Laura C E da Silva¹, Leonardo P Giglio¹, Tomás S Plivelic², Marcelo G de Oliveira³

Affiliations

¹ Institute of Chemistry, University of Campinas, UNICAMP, P.O. box 6154, 13083-970 Campinas, SP, Brazil.
² MAX IV Laboratory, Lund University, P. O. box 117, 221 00 Lund, Sweden.
³ Institute of Chemistry, University of Campinas, UNICAMP, P.O. box 6154, 13083-970 Campinas, SP, Brazil. Electronic address: mgo@unicamp.br.

PMID: 32470853
DOI: 10.1016/j.jcis.2020.05.049

Abstract

Hypothesis: Nitric oxide (NO)-releasing Pluronic F127 hydrogels (F127) containing dissolved S-nitrosothiols or pendant N-diazeniumdiolate (NONOate) groups have been described. The NO charging of these hydrogels is usually limited by their low stability or disruption of the micellar packing. S-nitrosothiol-terminated F127 may emerge as a new strategy for allowing NO delivery at different rates in biomedical applications.

Experiments: Terminal hydroxyl groups of F127 were esterified and reduced to produce F127-mercaptopropionate (HS-F127-SH), which was subsequently S-nitrosated to generate S-nitrosothiol-terminated F127 (ONS-F127-SNO). Micro-differential scanning calorimetry, ¹H NMR spin-spin relaxation (T₂), temperature-dependent small-angle X-ray scattering, and cryo-transmission electron microscopy, were used to determine the micellar packing structure, while real-time chemiluminescence NO detection and UV-Vis spectrophotometry were used to evaluate the kinetics of NO release.

Findings: HS-F127-SH micellization and gelation processes were analogous to native F127, however, with a decreased short-range ordering of the micelles. ONS-F127-SNO hydrogels released NO thorough a preferentially intramicellar SNO dimerization reaction. Increasing ONS-F127-SNO concentration reduces the rate of SNO dimerization and increases the overall rate of NO release to the gas phase, opening up new possibilities for tailoring NO delivery from F127-based hydrogels.

Keywords: Cryo TEM; Hydrogel; Microstructure; Nitric oxide; Pluronic F127; Reactive micelles; S-nitrosothiol; SAXS.