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

Abstract

Crosslinked polyesters with Young’s moduli similar to that of certain soft biological tissues were prepared via 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 S-nitrosothiol (RSNO) analogues by reaction with tert-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 S-nitrosated analogues were confirmed against Escherichia coli and Staphylococcus aureus. 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 S-nitrosated derivatives and suggested that the materials have appropriate Young’s moduli and elongation values for biomedical applications.

Synthetic Approaches to Combine the Versatility of the Thiol Chemistry with the Degradability of Aliphatic Polyesters

“…[67] Recently, the possibility of chemoselective synthesis of thiolated polyesters by condensation of thiomalic acid in the absence of catalyst has also been demonstrated. [68] A synthetic approach that enabled the synthesis of functionalized poly(lactic acid) bearing thiol-protected groups along the polymeric chain by condensation of related functional hydroxyl acids and lactic acid was also developed (Figure 16). [69] The functionalized hydroxyl acids were obtained by reaction of the desired thiols with the methyl oxirane-2-carboxylate.…”

Pair of Functional Polyesters That Are Photo-Cross-Linkable and Electrospinnable to Engineer Elastomeric Scaffolds with Tunable Structure and Properties

“…Thiomalic acid has been used to make sodium aurothiomalate in the treatment of rheumatoid arthritis . This monomer has also been used to synthesize thiol-bearing polyesters such as poly­(1,8-octanediol- co -citrate- co -thiomalate) and poly­(1,8-octanediol- co -maleicate- co -thiomalate) for biomedical applications . The other monomers such as glycerol, 1,8-octanediol, and sebacic acid have been used to make bioresorbable polyesters of poly­(glycerol sebacate) (PGS) and poly­(1,8-octanediol citrate) (POC). − Therefore, these selected monomers can ensure our designed elastomers are biocompatible and bioresorbable.…”

Long-Term Storage Stability and Nitric Oxide Release Behavior of (N-Acetyl-S-nitrosopenicillaminyl)-S-nitrosopenicillamine-Incorporated Silicone Rubber Coatings

“…The short half-life and poor stability of NO donating materials have been two concerns for their application in fabricating biomedical devices that have long indwelling lifetimes. In recent years, considerable efforts have been made for the development of stable NO-releasing materials, particularly utilizing molecules including N -diazeniumdiolates (NONOates) , and S -nitrosothiols (RSNOs), − and exploring their biomedical applications for the development of antimicrobial and hemocompatible coatings, catheter lock solutions, hydrogels, and biomedical devices with sustained NO release properties. ,− Incorporation of NO-releasing materials in polymer matrices can also enhance their stability through intramolecular hydrogen bonding and the formation of a polymer-crystal composite. ,, Further developments have covalently conjugated the NO donor moiety to the polymer backbone, which is one of the most promising ways to develop stable NO donating materials with prolonged and sustained NO release behavior in the physiological range (NO flux of 0.5 × 10 –10 to 4 × 10 –10 mol cm –2 min –1 ). − However, these materials have required a multistep synthesis and purification process and are thus less economically viable than the physical incorporation of NO donors into polymer matrices for device fabrication. − …”