More Lipophilic Dialkyldiamine-Based Diazeniumdiolates:  Synthesis, Characterization, and Application in Preparing Thromboresistant Nitric Oxide Release Polymeric Coatings

Abstract

The synthesis, characterization, and biomedical application in preparing more thromboresistant polymeric coatings for a series of lipophilic dialkyldiamine-based diazeniumdiolatesare described. Dialkylhexamethylenediamine diazeniumdiolates of the form RN[N(O)NO](-)(CH(2))(6)NH(2)(+)R, where R = CH(3), CH(2)CH(3), (CH(2))(2)CH(3), (CH(2))(3)CH(3), (CH(2))(4)CH(3,) (CH(2))(5)CH(3), and (CH(2))(11)CH(3), are prepared via reaction of the corresponding diamine with NO. The more lipophilic diazeniumdiolates [e.g., R = (CH(2))(3)CH(3)] can be incorporated into hydrophobic polymeric films (e.g., plasticized PVC), and the resulting materials release NO for extended periods of time upon exposure to PBS buffer. The mechanism of NO release from these films is examined in detail. More stable initial NO release can be achieved by adding lipophilic anionic species (e.g., tetraphenylborate derivative) to the polymeric material to buffer the activity of protons within the organic phase. It is shown that the use of these new lipophilic NO-donors in polymers provides the ability to tailor NO release rates for a variety of medical applications. As an example, polymers doped with N,N'-dibutylhexamethylenediamine diazeniumdiolate and a tetraphenylborate derivative are employed as coatings for vascular grafts in sheep. The NO release grafts exhibited enhanced performance and had an average 95% thrombus-free surface area compared to 42% for the corresponding control grafts when examined after 21d of implantation.

Mediation ofin vivo glucose sensor inflammatory response via nitric oxide release

“…The KTpClPB functions to buffer the proton activity within the membrane to modulate the release of NO, thus extending the NO release time. 25 Within 24 h after fabrication, the NOr sensors were sealed in tubes under nitrogen to preserve NO release function until use. To prevent any loss of NO release function, NOr sensors were not sterilized; however, they were fabricated under sterile conditions in a clean room.…”

“…25,26 The decomposition of the DBHD/ N 2 O 2 within the polymer film exposed to an aqueous environment, as found in tissue, releases two NO molecules (Fig. 1).…”

Diazeniumdiolate reactivity in model membrane systems

“…Because of the widespread use of diazeniumdiolates for targeting NO at specific biological sites and cell types [1,2], there is an interest in the nature of their interactions with complex environments encountered biologically and how such interactions influence their NO release rates [3][4][5]. Since both unilamellar and multilamellar phospholipid vesicles have been used extensively as models for bilayer membranes in studies of a variety of membrane-mediated processes, we have employed phospholipid liposomes as biomimetic media to explore the effect of different lipid interfaces and bilayer structures on diazeniumdiolate reactivity.…”

Modulated nitric oxide delivery in three-dimensional biomaterials for vascular functionality

“…One approach is to incorporate NO donors physically into a host material, of which the release profile of NO depends on the type of NO donor, [60] the characteristics of host materials (e.g., the water uptake rate for polymers), [61] and the interaction between the additive and host materials. [62] The other approach is to immobilize NO donors or NO-donating groups on a host material via covalent bonding. A slow and localized release of NO can also be achieved depending on the type of functional immobilization and the properties of the host material.…”