S-Nitrosated biodegradable polymers for biomedical applications: synthesis, characterization and impact of thiol structure on the physicochemical properties

Abstract

A new class of nitric oxide (NO)-releasing biodegradable polymers has been synthesized by derivatizing poly(lactic-co-glycolic-co-hydroxymethyl propionic acid) (PLGH) polymers with structurally unique thiol functionalities followed by nitrosation with t-butyl nitrite to yield pendant S-nitrosothiol moieties. The extent of thiolation was found to be dependent on the thiol moiety itself with the efficiency of incorporation as follows: cysteamine > cysteine > homocysteine. Glutathione and penicillamine were not incorporated to any significant extent. The structure and polymer environment associated with the pendant thiol has been related to the physicochemical properties of the resulting polymers. To quantify the extent of S-nitrosation, chemiluminescence and UV-visible spectroscopy techniques were employed in combination. The cysteamine and homocysteine derivatives were found to have the highest extent of nitrosation at 93 AE 3% and 96 AE 3%, respectively, followed by 43 AE 1% for cysteine. Thermal decomposition led to near-complete recovery of NO based upon the quantification of the RSNO formation for each nitrosated polymer. Our ability to exert control over the thiol structure, extent of incorporation and the subsequent nitrosation is crucial to the resulting range of NO release kinetics that were yielded. The functional utility of these materials is demonstrated in that these non-toxic polymers release NO under physiological conditions, have degradation profiles that are appropriate for tissue scaffolds and can be prepared as electrospun nanofibers, commonly used in tissue and bone regeneration applications.

Antimicrobial Activity of Nitric Oxide-Releasing Ti-6Al-4V Metal Oxide

“…The synthesis of the S -nitrosothiol donor was confirmed using UV-VIS, where the wavelength of maximum absorbance at 340 nm matches that of the characteristic SNO group of other well characterized S -nitrosothiol donors (Figure 2) [46,47,52]. The UV-VIs spectrum of unbound S -nitroso-penicillamine lacks contributions from excess nitrite and nitrous acid from the synthesis step and, thus, could be utilized in further reactions and NO release assays [53].…”

Bio-inspired strategies for designing antifouling biomaterials

“…For this reason, endothelium is one of the most thromboresisitive materials. Consequently, materials that can release NO at a steady-state equivalent to that released by the natural endothelium (0.5 × 10 −10 mol cm −2 min −1 ) [ 15 ], can be a suitable material for making biomedical devices with enhanced antifouling capabilities [ 16 , 17 ]. Liu et al recently demonstrated that the presence of NO significantly reduces the formation of Shewanella woodyi ( S. woodyi ) biofilm by simultaneously down-regulating the cyclase activity and up-regulating the phosphodiesterase activity of the diguanylate cyclase gene ( Sw DGC) (Fig.…”

Nitric Oxide Donors for Cardiovascular Implant Applications

“…Both are naturally occurring substances in the human body and do not affect normal cell function 67. A new class of biodegradable polymer for NO release has been used for incorporation of RSNOs in to poly(lactic‐ co ‐glycolic‐ co ‐hydroxymethyl propionic acid) (PLGH) 68. Depending on the type of –SH moieties pendant to the polymer backbone, the amounts of NO donor (0.17 and 0.53 mmol SNO g −1 polymer) and its release profile (0.033 and 0.241 mmol NO g −1 polymer) can be controlled and sustained over a 48 h period in vitro ( Figure ).…”

“…For comparison, the lower‐limit NO flux released by natural ECs is indicated by the black dashed line. Adapted with permission 68. Copyright 2012, Royal Society of Chemistry.…”