Therapeutic Delivery of Nitric Oxide Utilizing Saccharide-Based Materials

Abstract

As a gasotransmitter, nitric oxide (NO) regulates physiological pathways and demonstrates therapeutic effects such as vascular relaxation, anti-inflammation, antiplatelet, antithrombosis, antibacterial, and antiviral properties. However, gaseous NO has high reactivity and a short half-life, so NO delivery and storage are critical questions to be solved. One way is to develop stable NO donors and the other way is to enhance the delivery and storage of NO donors from biomaterials. Most of the researchers studying NO delivery and applications are using synthetic polymeric materials, and they have demonstrated significant therapeutic effects of these NO-releasing polymeric materials on cardiovascular diseases, respiratory disease, bacterial infections, etc. However, some researchers are exploring saccharide-based materials to fulfill the same tasks as their synthetic counterparts while avoiding the concerns of biocompatibility, biodegradability, and sustainability. Saccharide-based materials are abundant in nature and are biocompatible and biodegradable, with wide applications in bioengineering, drug delivery, and therapeutic disease treatments. Saccharide-based materials have been implemented with various NO donors (like S-nitrosothiols and N-diazeniumdiolates) via both chemical and physical methods to deliver NO. These NOreleasing saccharide-based materials have exhibited controlled and sustained NO release and demonstrated biomedical applications in various diseases (respiratory, Crohn's, cardiovascular, etc.), skin or wound applications, antimicrobial treatment, bone regeneration, anticoagulation, as well as agricultural and food packaging. This review aims to highlight the studies in methods and progress in developing saccharide-based NO-releasing materials and investigating their potential applications in biomedical, bioengineering, and disease treatment.

S-Nitroso-N-acetylpenicillamine grafted silicone oil for antibacterial interface applications

“…Covalently conjugated NO donor with polymers could avoid the leaching issues by avoiding excessive donor leaching, lowering the initial NO release flux, and tend to have long-term NO release. 35 Therefore, covalent linkage of NO to polymer structure can enhance the localized delivery of NO, which is an important concern in medical device field.…”

Recent Developments in Multifunctional Antimicrobial Surfaces and Applications toward Advanced Nitric Oxide-Based Biomaterials

“…The use of materials that release nitric oxide (NO) has become a popular strategy to simultaneously overcome the issues arising from the use of biomedical devices, including the issue of biofilms. − NO is a diatomic free radical, gaseous transmitter molecule that is endogenously produced in the body when l -arginine undergoes enzymatic oxidation in the presence of nitric oxide synthase (NOS), resulting in the production of NO and l -citrulline. , Healthy endothelial cells generate a NO flux of (0.5–4) × 10 –10 mol cm –2 min –1 in the blood vessels that protects against platelet activation and aggregation, exhibits an antiproliferative effect on smooth muscle cells (SMCs), and controls vasodilation and blood pressure . Nitric oxide is known to regulate many physiological functions such as neurotransmission, vasodilation, immune response to infection, wound healing, angiogenesis, and oxygen-free radical generation. , Apart from these versatile properties, NO has also been found to possess excellent antimicrobial/bactericidal activity against both Gram-positive and Gram-negative bacteria, including several clinically resistant bacteria strains such as methicillin-resistant S. aureus (MRSA). − The antibacterial activity of NO is governed by multiple mechanisms such as nitrosation of amines and thiols, chemical alteration of DNA, lipid peroxidation, promotion of iron depletion in bacteria, and tyrosine nitration. − Moreover, NO has a very short half-life in the physiological environment, which makes its action very rapid, and as a result, bacteria are unable to develop resistance against NO. , These properties of NO make it a superior therapeutic compared with traditional antibiotics or other active antimicrobial agents discussed above.…”

“…135 oxygen-free radical generation. 136,137 Apart from these versatile properties, NO has also been found to possess excellent antimicrobial/bactericidal activity against both Gram-positive and Gram-negative bacteria, including several clinically resistant bacteria strains such as methicillin-resistant S. aureus (MRSA). 138−140 The antibacterial activity of NO is governed by multiple mechanisms such as nitrosation of amines and thiols, chemical alteration of DNA, lipid peroxidation, promotion of iron depletion in bacteria, and tyrosine nitration.…”

A Supramolecular Nitric Oxide Nanodelivery System for Prevention of Tumor Metastasis by Inhibiting Platelet Activation and Aggregation

“…Nitric oxide (NO), an endogenous signal molecule, participates in various physiological and pathological processes. − Owing to its multiple functions, NO becomes prevalent in the treatment of many diseases, such as cardiovascular diseases, tumors, bacterial infections, etc. − It should be noted that NO is an important antiplatelet agent in the human body by a cGMP-dependent pathway. , Therefore, NO can be used to prevent thrombosis and atherosclerosis by the blockage of platelet coagulation, and it might also be promising to inhibit TCIPA. − Various NO donors and nanodelivery systems were developed for NO-based gas therapy. − However, the high reactivity of NO limits the practical applications of NO donors . The precise delivery of NO is especially important to exert its pharmacological activities.…”