title: Micelles for delivery of nitric oxide.
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.
authors.affiliation: Institute of Bioengineering (IBI), Ecole Polytechnique Federale de Lausanne, Lausanne CH 1015, Switzerland.
authors.forename: Yun Suk
authors.initials: YS
authors.lastname: Jo
authors.forename: André J
authors.initials: AJ
authors.lastname: van der Vlies
authors.forename: Jay
authors.initials: J
authors.lastname: Gantz
authors.forename: Tyler N
authors.initials: TN
authors.lastname: Thacher
authors.forename: Sasa
authors.initials: S
authors.lastname: Antonijevic
authors.forename: Simone
authors.initials: S
authors.lastname: Cavadini
authors.forename: Davide
authors.initials: D
authors.lastname: Demurtas
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Stergiopulos
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Hubbell
mesh_terms: D000180:Acrylic Resins / Q000138:chemical synthesis / Q000737:chemistry*; D001391:Azo Compounds / Q000737:chemistry; D008823:Micelles; D009569:Nitric Oxide / Q000737:chemistry*; D020030:Nitric Oxide Donors / Q000138:chemical synthesis / Q000737:chemistry*; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D000180:Acrylic Resins; D001391:Azo Compounds; D008823:Micelles; D020030:Nitric Oxide Donors; D010879:Piperazines; C452539:diazeniumdiolate; C015460:poly(acryloylmorpholine); D009569:Nitric Oxide