Sustained Nitric Oxide Release from a Tertiary S-Nitrosothiol-based Polyphosphazene Coating.

Nitric oxide (NO) occurs naturally in mammalian biochemistry as a critical signaling molecule and exhibits antithrombotic, antibacterial, and wound-healing properties. NO-forming biodegradable polymers have been utilized in the development of antithrombotic or antibacterial materials for biointerfacial applications, including tissue engineering and the fabrication of erodible coatings for medical devices such as stents. Use of such NO-forming polymers has frequently been constrained by short-term release or limited NO storage capacity and has led to the pursuit of new materials with improved NO release function. Herein, we report the development of an NO-releasing bioerodible coating prepared from poly[bis(3-mercapto-3-methylbut-1-yl glycinyl)phosphazene] (POP-Gly-MMB), a polyphosphazene based on glycine and the naturally occurring tertiary thiol 3-mercapto-3-methylbutan-1-ol (MMB). To evaluate the NO release properties of this material, the thiolated polymer POP-Gly-MMB-SH was applied as a coating to glass substrates and subsequently converted to the NO-forming S-nitrosothiol (RSNO) derivative (POP-Gly-MMB-NO) by immersion in a mixture of tert-butyl nitrite (t-BuONO) and pentane. NO release flux from the coated substrates was determined by chemiluminescence-based NO measurement and was found to remain in a physiologically relevant range for up to 2 weeks (6.5-0.090 nmol of NO·min