Micelles for delivery of nitric oxide

Yun Suk Jo, Andréj Van Der Vlies, Jay Gantz, Tyler N. Thacher, Sasa Antonijevic, Simone Cavadini, Davide Demurtas, Nikolaos Stergiopulos, Jeffrey A. Hubbell

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

We designed block copolymer pro-amphiphiles and amphiphiles for providing very long-term release of nitric oxide (NO). A block copolymer of N-acryloylmorpholine (AM, as a hydrophile) and N-acryloyl-2,5-dimethylpiperazine (AZd, as a hydrophilic precursor) was synthesized. The poly(N-acryloyl-2,5- dimethylpiperazine) (PAZd) is water-soluble, but chemical reaction of the secondary amines with NO to form a N-diazeniumdiolate (NONOate) converts the hydrophilic PAZd into a hydrophobic poly(sodium-1-(N-acryloyl-2,5- dimethylpiperazin-1-yl)diazen-1-ium-1,2-diolate) (PAZd·NONOate), driving aggregation. The PAM block guides this process toward micellization, rather than precipitation, yielding ca. 50 nm spherical micelles. The hydrophobic core of the micelle shielded the NONOate from the presence of water, and thus protons, which are required for NO liberation, delaying release to a remarkable 7 d half-life. Release of the NO returned the original soluble polymer. The very small NO-loaded micelles were able to penetrate complex tissue structures, such as the arterial media, opening up a number of tissue targets to NO-based therapy.

Original languageEnglish
Pages (from-to)14413-14418
Number of pages6
JournalJournal of the American Chemical Society
Volume131
Issue number40
DOIs
StatePublished - Oct 14 2009
Externally publishedYes

Fingerprint

Nitric oxide
Micelles
Nitric Oxide
Amphiphiles
Block copolymers
Tissue
Tunica Media
Pulse amplitude modulation
Micellization
Water
Amines
Half-Life
Protons
Chemical reactions
Polymers
Agglomeration
Sodium

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Jo, Y. S., Van Der Vlies, A., Gantz, J., Thacher, T. N., Antonijevic, S., Cavadini, S., ... Hubbell, J. A. (2009). Micelles for delivery of nitric oxide. Journal of the American Chemical Society, 131(40), 14413-14418. https://doi.org/10.1021/ja905123t

Micelles for delivery of nitric oxide. / Jo, Yun Suk; Van Der Vlies, Andréj; Gantz, Jay; Thacher, Tyler N.; Antonijevic, Sasa; Cavadini, Simone; Demurtas, Davide; Stergiopulos, Nikolaos; Hubbell, Jeffrey A.

In: Journal of the American Chemical Society, Vol. 131, No. 40, 14.10.2009, p. 14413-14418.

Research output: Contribution to journalArticle

Jo, YS, Van Der Vlies, A, Gantz, J, Thacher, TN, Antonijevic, S, Cavadini, S, Demurtas, D, Stergiopulos, N & Hubbell, JA 2009, 'Micelles for delivery of nitric oxide', Journal of the American Chemical Society, vol. 131, no. 40, pp. 14413-14418. https://doi.org/10.1021/ja905123t
Jo YS, Van Der Vlies A, Gantz J, Thacher TN, Antonijevic S, Cavadini S et al. Micelles for delivery of nitric oxide. Journal of the American Chemical Society. 2009 Oct 14;131(40):14413-14418. https://doi.org/10.1021/ja905123t
Jo, Yun Suk ; Van Der Vlies, Andréj ; Gantz, Jay ; Thacher, Tyler N. ; Antonijevic, Sasa ; Cavadini, Simone ; Demurtas, Davide ; Stergiopulos, Nikolaos ; Hubbell, Jeffrey A. / Micelles for delivery of nitric oxide. In: Journal of the American Chemical Society. 2009 ; Vol. 131, No. 40. pp. 14413-14418.
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