A novel dendritic mesoporous silica based sustained hydrogen sulfide donor for the alleviation of adjuvant-induced inflammation in rats

PURPOSE: S-propargyl-cysteine (SPRC), an excellent endogenous hydrogen sulfide (H(2)S) donor, could elevate H(2)S levels via the cystathionine γ-lyase (CSE)/H(2)S pathway both in vitro and in vivo. However, the immediate release of H(2)S in vivo and daily administration of SPRC potentially limited its clinical use. METHODS: To solve the fore-mentioned problem, in this study, the dendritic mesoporous silica nanoparticles (DMSN) was firstly prepared, and a sustained H(2)S delivery system consisted of SPRC and DMSN (SPRC@DMSN) was then constructed. Their release profiles, both in vitro and in vivo, were investigated, and their therapeutical effect toward adjuvant-induced arthritis (AIA) rats was also studied. RESULTS: The spherical morphology of DMSN could be observed under scanning Electron Microscope (SEM), and the transmission electron microscope (TEM) images showed a central-radiational pore channel structure of DMSN. DMSN showed excellent SPRC loading capacity and attaining a sustained releasing ability than SPRC both in vitro and in vivo, and the prolonged SPRC releasing could further promote the release of H(2)S in a sustained manner through CSE/H(2)S pathway both in vitro and in vivo. Importantly, the SPRC@DMSN showed promising anti-inflammation effect against AIA in rats was also observed. CONCLUSIONS: A sustained H(2)S releasing donor consisting of SPRC and DMSN was constructed in this study, and this sustained H(2)S releasing donor might be of good use for the treatment of AIA.