Characterization of an S-nitroso-N-acetylpenicillamine–based nitric oxide releasing polymer from a translational perspective

Abstract

Due to the role of nitric oxide (NO) in regulating a variety of biological functions in humans, numerous studies on different NO releasing/generating materials have been published over the past two decades. Although NO has been demonstrated to be a strong antimicrobial and potent antithrombotic agent, NO-releasing (NOrel) polymers have not reached the clinical setting. While increasing the concentration of the NO donor in the polymer is a common method to prolong the NO-release, this should not be at the cost of mechanical strength or biocompatibility of the original material. In this work, it was shown that the incorporation of S-nitroso-penicillamine (SNAP), an NO donor molecule, into Elast-eon E2As (a copolymer of mixed soft segments of polydimethylsiloxane and poly(hexamethylene oxide)), does not adversely impact the physical and biological attributes of the base polymer. Incorporating 10 wt % of SNAP into E2As reduces the ultimate tensile strength by only 20%. The inclusion of SNAP did not significantly affect the surface chemistry or roughness of E2As polymer. Ultraviolet radiation, ethylene oxide, and hydrogen peroxide vapor sterilization techniques retained approximately 90% of the active SNAP content, where sterilization of these materials did not affect the NO-release profile over an 18 day period. Furthermore, these NOrel materials were shown to be biocompatible with the host tissues as observed through hemocompatibility and cytotoxicity analysis. In addition, the stability of SNAP in E2As was studied under a variety of storage conditions, as they pertain to translational potential of these materials. SNAP-incorporated E2As stored at room temperature for over 6 months retained 87% of its initial SNAP content. Stored and fresh films exhibited similar NO release kinetics over an 18 day period. Combined, the results from this study suggest that SNAPdoped E2As polymer is suitable for commercial biomedical applications due to the reported physical and biological characteristics that are important for commercial and clinical success.

A multi-defense strategy: Enhancing bactericidal activity of a medical grade polymer with a nitric oxide donor and surface-immobilized quaternary ammonium compound

“…The incorporation of SNAP in medical grade polymers have been shown to be hemocompatible and possesses stability during long-term storage at room temperature and physiological conditions [63, 72, 73]. …”

“…Another report has also shown that hydrophobic polymers with SNAP have extended NO-release at physiological levels (up to 20 days) [70]. Furthermore, the incorporation of SNAP in medical grade polymers are not only hemocompatible and biocompatible but also stable during long-term storage (6 months) at room temperature [63, 72, 73]. …”

“…The realization of the immense potential of NO in creating biomimetic materials has encouraged researchers to synthesize several NO donor molecules to allow the storage and local delivery of NO at the material surface. S -nitroso- N acetylpenicillamine (SNAP) is one such NO donor that has widely been used in developing NO-releasing materials [43, 52, 60–63]. In the past, Worley et al , have demonstrated the (NO)-releasing quaternary ammonium (QA)-functionalized generation 1 (G1) and generation 4 (G4) poly(amidoamine) (PAMAM) dendrimers using N -diazonium diolate NO donors [32].…”

Enhanced antibacterial efficacy of nitric oxide releasing thermoplastic polyurethanes with antifouling hydrophilic topcoats

“…35, 41–61 It is a free radical that reacts with superoxides and oxygen to form peroxynitrite and dinitrogen trioxide, respectively. 42, 43, 62 Nitric oxide’s mechanisms of action against bacteria include nitrosation of amines and thiols in the extracellular matrix, lipid peroxidation and tyrosine nitration in the cell wall, and DNA cleavage in the cellular matrix.…”

Attenuation of thrombosis and bacterial infection using dual function nitric oxide releasing central venous catheters in a 9 day rabbit model

“…Many NO donors such as S -nitrosothiols [33, 34] and N-diazeniumdiolates [35, 36] have been developed and studied for their potential to locally release NO from polymer surfaces. The addition of NO donors into polymeric materials has been shown to be non-cytotoxic and non-hemolytic, while maintaining the mechanical properties of the base polymer [37]. …”