Biodegradable crosslinked polyesters derived from thiomalic acid and S -nitrosothiol analogues for nitric oxide release

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2018-06, Vol.6 (24), p.4071-4081
• Main Authors: Yapor, Janet P, Neufeld, Bella H, Tapia, Jesus B, Reynolds, Melissa M
• Format: Article
• Language: English
• Subjects: Acids; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - pharmacology; Biodegradability; Biodegradable Plastics - chemical synthesis; Biodegradable Plastics - pharmacology; Biodegradation; Biomedical materials; Chemiluminescence; Citric acid; Citric Acid - chemistry; Conjugation; Crosslinking; Degradation products; E coli; Elastic Modulus; Elongation; Escherichia coli - drug effects; Hydrogen-Ion Concentration; Ions; Maleates - chemistry; Maleic acid; Mass spectrometry; Mass spectroscopy; Mechanical tests; Modulus of elasticity; Nitric oxide; Nitric Oxide - chemistry; Nitric Oxide Donors - chemical synthesis; Nitric Oxide Donors - pharmacology; Octanols - chemistry; Organic chemistry; pH effects; Polyester resins; Polyesters; Polyesters - chemical synthesis; Polyesters - pharmacology; Polymerization; Polymers; S-Nitrosothiols - chemistry; Staphylococcus aureus - drug effects; Temperature; Thiomalates - chemistry; Tissues
• ISSN: 2050-750X; 2050-7518
• DOI: 10.1039/c8tb00566d

Crosslinked polyesters with Young's moduli similar to that of certain soft biological tissues were prepared bulk polycondensation of thiomalic acid and 1,8-octanediol alone, and with citric or maleic acid. The copolymers were converted to nitric oxide (NO)-releasing -nitrosothiol (RSNO) analogues by reaction with -butyl nitrite. Additional conjugation steps were avoided by inclusion of the thiolated monomer during the polycondensation to permit thiol conversion to RSNOs. NO release at physiological pH and temperature (pH 7.4, 37 °C) was determined by chemiluminescence-based NO detection. The average total NO content for poly(thiomalic-co-maleic acid-co-1,8-octanediol), poly(thiomalic-co-citric acid-co-1,8-octanediol), and poly(thiomalic acid-co-1,8-octanediol) was 130 ± 39 μmol g-1, 200 ± 35 μmol g-1, and 130 ± 11 μmol g-1, respectively. The antibacterial properties of the -nitrosated analogues were confirmed against and . The hydrolytic degradation products were analyzed by time-of-flight mass spectrometry after a 10-week study to investigate their composition. Tensile mechanical tests were performed on the non-nitrosated polymers as well as their -nitrosated derivatives and suggested that the materials have appropriate Young's moduli and elongation values for biomedical applications.