Table 4.
Comparison of advantages and disadvantages of each NO-donor and NO-delivering polymeric material design.
| NO Donors/Polymeric Materials | Advantages | Disadvantages |
|---|---|---|
| NO gas | FDA approved; Direct NO delivery to lung infection sites and surface of wound infections; Side effects easily reversed by stopping NO gas | React with oxygen to give potent pulmonary irritants like NO2 and with hemoglobin to give methemoglobin |
| Metal-nitrosyl complexes | Metal-nitrosyl complexes, such as sodium nitroprusside (SNP), is FDA approved and long history of use clinically |
Possibility of cyanide toxicity when using SNP for prolonged treatment |
| Ru-nitrosyl complexes | Photo-responsive | Relatively new and less well studied for antimicrobial purposes |
| S-nitrosothiols (RSNO) | Present endogenously; Some, such as GSNO, have well studied metabolism and low toxicity; NO release can be modulated through various means, including light irradiation; Easily incorporated into polymeric scaffold | Spontaneous release of NO and formation of disulfide bonds in solution; Trans-nitrosylation reaction with other thiol groups present in the body; Multiple mechanisms of degradation by bacteria |
| N-diazeniumdiolates (NONOates) | Broad range of reproducible NO release kinetics; Easily incorporated into polymeric materials containing amine moieties by passing NO gas at high pressure; Stable in powder form and in alkaline solutions |
Spontaneous NO release in solution under physiological conditions. Not used clinically |
| Furoxans | Well-studied NO release with applications in various NO mediated biological processes; Prolong duration of action compared to other NO donors; Thermally stable; May be conjugated to other groups for codelivery of antimicrobials and NO donor | Appears to have other non-NO dependent effects on evaluated bacteria (i.e., P. aeruginosa) that is not well studied or explained with NO release |
| Hybrid NO donor | Targeted NO release using antibiotics or antimicrobial peptides; Synergistic effect at eradicating bacteria/biofilm with both targeted NO release and QS inhibition or antimicrobial action | Earlier generations of some hybrid NO donors, such as C3D, require induction of β-lactamase production for activity |
| NO-releasing polymeric materials | ||
| Chitosan-based NO-releasing materials | Chitosan scaffold is biodegradable, biocompatible and has innate antimicrobial activity; Cationic chitosan promotes association with negatively charged bacterial membranes; Primary amine groups offer a straightforward means of incorporating NO-releasing moieties | In cases like NO-releasing chitosan oligosaccharide (COS/NO), cationic chitosan may improve cohesion of negatively charged biofilms |
| Alginate-based NO-releasing materials | Alginate is biodegradable and biocompatible; NO-releasing moieties easily introduced via abundant hydroxyl and carboxylic acid groups; NO release easily tunable by modifying high/low molecular weight alginate used | |
| NO-releasing cyclodextrins | Hydrophobic central cavity and hydrophilic exterior could enable delivery of hydrophobic antimicrobial compounds along with NO release | |
| NO-releasing silica nanoparticles | Innate antimicrobial activity of nanoparticles. Physiochemical properties, such as shape, sizes, and surface charge can be easily modified to improve NO delivery and bacteria eradication | Cytotoxicity reported in some designs |
| NO-releasing polymeric nanoparticles | Specificity and controlled release of NO can be achieved by incorporating photo-responsive groups and surface-charge switchable components; Able to co-deliver antibiotic with NO release to enhance bacterial or biofilm eradication; Other properties, e.g., magnetic field responsive NO-NP, may also be obtained | |
| NO-releasing dendrimers | High NO payloads within a single framework; Polymerization of antibiotics enable simultaneous delivery of NO with antibiotic and improve bacteria and biofilm eradication | Cytotoxicity may be associated with higher generation dendrimers and certain chemical modifications/ dendrimers |
| NO-releasing gel, polymer, and coatings | NO-releasing surfaces used in blood contacting medical devices may be designed to generate an NO flux representative of endothelial cells; Additional coating along with NO release can extent the anti-fouling lifespan of the material | Leaching of NO may occur depending on the design |