Nitric oxide (NO) is involved in physiological processes, including vasodilatation, wound healing and antibacterial activities. As NO is a free radical, designing drugs to generate therapeutic amounts of NO in controlled spatial and time manners is still a challenge. In this study, the NO donor S-nitrosoglutathione (GSNO) was incorporated into the thermoresponsive Pluronic F-127 (PL)-chitosan (CS) hydrogel, with an easy and economically feasible methodology. CS is a polysaccharide with known antimicrobial properties. Scanning electron microscopy, rheology and differential scanning calorimetry techniques were used for hydrogel characterization. The results demonstrated that the hydrogel has a smooth surface, thermoresponsive behavior and good mechanical stability. The kinetics of NO release and GSNO diffusion from GSNO-containing PL/CS hydrogel demonstrated a sustained NO/GSNO release, in concentrations suitable for biomedical applications. The GSNO-PL/CS hydrogel demonstrated a concentration-dependent toxicity to Vero cells, and antimicrobial activity to Pseudomonas aeruginosa (minimum inhibitory concentration and minimum bactericidal concentration values of 0.5 µg·mL−1 of hydrogel, which corresponds to 1 mmol·L−1 of GSNO). Interestingly, the concentration range in which the NO-releasing hydrogel demonstrated an antibacterial effect was not found to be toxic to the Vero mammalian cell. Thus, the GSNO-PL/CS hydrogel is a suitable biomaterial for topical NO delivery applications.

Because of their antibacterial activity, silver nanoparticles (AgNPs) have been explored in biomedical applications. Similarly, nitric oxide (NO) is an important endogenous free radical with an antimicrobial effect and toxicity toward cancer cells that plays pivotal roles in several processes. In this work, biogenic AgNPs were prepared using green tea extract and the principles of green chemistry, and the NO donor S-nitrosoglutathione (GSNO) was prepared by the nitrosation of glutathione. To enhance the potentialities of GSNO and AgNPs in biomedical applications, the NO donor and metallic nanoparticles were individually or simultaneously incorporated into polymeric solid films of poly­(vinyl alcohol) (PVA) and poly­(ethylene glycol) (PEG). The resulting solid nanocomposites were characterized by several techniques, and the diffusion profiles of GSNO and AgNPs were investigated. The results demonstrated the formation of homogeneous PVA/PEG solid films containing GSNO and nanoscale AgNPs that are distributed in the polymeric matrix. PVA/PEG films containing AgNPs demonstrated a potent antibacterial effect against Gram-positive and Gram-negative bacterial strains. GSNO-containing PVA/PEG films demonstrated toxicity toward human cervical carcinoma and human prostate cancer cell lines. Interestingly, the incorporation of AgNPs in PVA/PEG/GSNO films had a superior effect on the decrease of cell viability of both cancer cell lines, compared with cells treated with films containing GSNO or AgNPs individually. To our best knowledge, this is the first report to describe the preparation of PVA/PEG solid films containing GSNO and/or biogenically synthesized AgNPs. These polymeric films might find important biomedical applications as a solid material with antimicrobial and antitumorigenic properties.

Nitric oxide (NO) and silver nanoparticles (AgNPs) are well-known for their antibacterial activity. In this work, S-nitroso-mercaptosuccinic acid (S-nitroso-MSA), a NO donor, and green tea synthesized AgNPs were individually or simultaneously incorporated into alginate hydrogel for topical antibacterial applications. The obtained hydrogels were characterized and the NO release and diffusion of AgNPs and S-nitroso-MSA from alginate hydrogels were investigated. The hydrogels showed a concentration dependent toxicity toward Vero cells. The potent antibacterial effect of the hydrogels was demonstrated toward Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, and Streptococcus mutans UA159. Interestingly, the combination of S-nitroso-MSA and AgNPs into alginate hydrogels had a superior antibacterial effect, compared with hydrogels containing S-nitroso-MSA or AgNPs individually. This is the first report to describe the synthesis, cytotoxicity, and antibacterial effects of alginate hydrogel containing NO donor and AgNPs. These hydrogels might find important local applications in the combat of bacterial infections.

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