Nitric Oxide Releasing Delivery Platforms: Design, Detection, Biomedical Applications, and Future Possibilities

Abstract

Gasotransmitters belong to the subfamily of endogenous gaseous signaling molecules, which find a wide range of biomedical applications. Among the various gasotransmitters, nitric oxide (NO) has an enormous effect on the cardiovascular system. Apart from this, NO showed a pivotal role in neurological, respiratory, and immunological systems. Moreover, the paradoxical concentration-dependent activities make this gaseous signaling molecule more interesting. The gaseous NO has negligible stability in physiological conditions (37 °C, pH 7.4), which restricts their potential therapeutic applications. To overcome this issue, various NO delivering carriers were reported so far. Unfortunately, most of these NO donors have low stability, short half-life, or low NO payload. Herein, we review the synthesis of NO delivering motifs, development of macromolecular NO donors, their advantages/disadvantages, and biological applications. Various NO detection analytical techniques are discussed briefly, and finally, a viewpoint about the design of polymeric NO donors with improved physicochemical characteristics is predicted.

NO in Viral Infections: Role and Development of Antiviral Therapies

“…Several NO-donors, including SNAP and S -nitrosoglutathione (GSNO), have been incorporated into polymeric platforms [ 80 , 81 , 82 ]. The use of these macromolecular scaffolds was necessary to improve the physicochemical profiles of NO-donors and, thus, NO-delivery and targeting [ 81 , 83 , 84 ]. The architecture of the nanosystem, its biodegradation mechanism and the stimulus causing NO release were designed around the properties of the NO-donor to be incorporated and the organ or tissue to be targeted [ 83 , 84 , 85 , 86 , 87 , 88 ].…”

Nanomolar Nitric Oxide Concentrations in Living Cells Measured by Means of Fluorescence Correlation Spectroscopy

“…The unique chemical and physical properties of NO—reactivity, a short half-life, and fast diffusion—limit the therapeutic efficiency of NO gas, but a variety of donor compounds have been widely investigated, not only to exploit the NO physiology but also to extend the release possibilities [ 12 ]. The last few decades have led to the development of various nitrocompounds with specific segments able to facilitate NO release in different times and in the presence or absence of a trigger (e.g., pH, susceptibility to oxygen, light, and/or temperature) [ 13 ]. The most commonly used NO donors are low-molecular-weight compounds, including organic nitrates, diazeniumdiolates, S-nitrosothiols, stimuli-responsive N-nitrosamines, metal nitrosyl complexes, and furoxans [ 13 , 14 , 15 ].…”

“…The last few decades have led to the development of various nitrocompounds with specific segments able to facilitate NO release in different times and in the presence or absence of a trigger (e.g., pH, susceptibility to oxygen, light, and/or temperature) [ 13 ]. The most commonly used NO donors are low-molecular-weight compounds, including organic nitrates, diazeniumdiolates, S-nitrosothiols, stimuli-responsive N-nitrosamines, metal nitrosyl complexes, and furoxans [ 13 , 14 , 15 ]. The current therapeutic application of NO donors is limited by pharmacodynamics, pharmacokinetics (i.e., the level of absorption and toxicity), and NO’s bimodal pro- and antitumorigenic role [ 13 , 16 ].…”

“…The most commonly used NO donors are low-molecular-weight compounds, including organic nitrates, diazeniumdiolates, S-nitrosothiols, stimuli-responsive N-nitrosamines, metal nitrosyl complexes, and furoxans [ 13 , 14 , 15 ]. The current therapeutic application of NO donors is limited by pharmacodynamics, pharmacokinetics (i.e., the level of absorption and toxicity), and NO’s bimodal pro- and antitumorigenic role [ 13 , 16 ]. Great hope is placed in suitable NO carriers that will reach the right place, extend the life span of NO, and release the right amount of NO in a controlled manner.…”

“…Since the NO concentration is essential for its pro- or antitumorigenic effect (millimolar vs. pico- and nanomolar, respectively), and its rapid decomposition makes the detection process challenging, it is the responsibility of an appropriately sensitive and selective technique to verify the efficacy of NO delivery. Moreover, most detection techniques fail in obtaining precise NO measurements in a biological environment [ 13 ].…”