Abstract
S-nitrosothiols are a class of NO-donors currently under investigation for the treatment of various diseases. In this study, we developed a novel NO-donor (S-nitrosoglutathione-alginate, SNA) by cross-linking alginate with S-nitrosothiols, which can deliver NO in a sustained manner. This compound can be further evaluated for oral delivery to treat Crohn’s disease. This new compound was prepared using a two-step procedure involving (I) linkage of reduced glutathione to alginate and (II) post-nitrosation with sodium nitrite (NaNO2). The amount of linked thiol moieties for the possible nitrosation was calculated using Ellman’s method, and the amount of NO abducted on the polymer was calculated using the Griess–Saville method. An ex vivo model (i.e. Ussing chamber) was used to investigate the permeation of this new NO-donor across the rat intestinal barrier. We obtained polymers with different numbers of abducted NOs (174 ± 21 μmol/g for SNA F1 and 468 ± 23 μmol/g for SNA F2) depending on the procedure used for nitrosation. In the ex vivo studies in the Ussing chamber, SNA F2 exhibited a sustained release for at least 10 h. The effect of pH on the stability of the new compound was also investigated, and the new compound was more stable at a mildly basic pH of 8.4 where 73% remained after 1 week. However, only 50% remained after 1 week at an acidic pH of 1.2. In the cytotoxicity studies (Caco2), this compound was nontoxic at concentrations of less than 200 μM.
Acknowledgements
SU Shah wishes to acknowledge funding support by the Higher Education Commission of Pakistan.
Declaration of interest
The authors have no conflict of interest.