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

Abstract

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.

The Anti-Inflammation and Anti-Nociception Effect of Ketoprofen in Rats Could Be Strengthened Through Co-Delivery of a H2S Donor, S-Propargyl-Cysteine

“…Our previous study used SPRC with dosage of 100 mg kg −1 for the treatment of AIA in rats through subcutaneous injection or oral administration once q72h, which showed gratifying therapeutical effect, while the dosage of 50 mg kg −1 showed limited therapeutical effect. 55,58 However, in this study, we have different findings. In the SPRC group, we solely used SPRC at dosage of 50 mg kg −1 , consistent with our previous studies, there was no treatment effects could be observed.…”

“…The reason for the improved therapeutical effect was possibly through two aspects, for one aspect, the sustained release of SPRC from SK@MS might elevate the H 2 S concentration in vivo in a relevant stable level compared with SPRC powder. 58 , 69 For another aspect, the co-deliver of NSAIDs might also augment the therapeutical potency of SPRC.…”

“…The hind limb of rats in different groups were scanned and reconstructed as previously reported 58 via Siemens Inveon PET/CT (Siemens, Munich, Germany). The exposure time was set as 800 ms, while the voltage and electric current were set as 70 kV and 400 mA, respectively.…”

Signaling pathways in rheumatoid arthritis: implications for targeted therapy

“…463 SPRC might serve as a potential drug for RA treatment. We have developed two sustained-release donors of hydrogen sulfide, 464,465 which has solved the problem of hydrogen sulfide release too fast in conventional formulations. ZYZ-802 is filing for clinical trials by CFDA and FDA now.…”

Local delivery of gaseous signaling molecules for orthopedic disease therapy

“…The current effect of H 2 S-delivered nanomaterials for the treatment of diseases is mainly immunomodulatory or anti-inflammatory. Yu et al demonstrated a solution to the problem of premature release of the H 2 S donor S-propargylcysteine using polylactic acid (PLA) microspheres and dendritic mesoporous silica nanoparticles, achieved a slow release of H 2 S in vivo for up to 3 days, and observed improved adjuvant-induced arthritis scores, inflammatory factor indices, and imaging performance in rats [ 137 , 138 ]. S-Propargylcysteine exerts antioxidant effects through the upregulation of the Nrf2-antioxidant response element (ARE) signaling pathway, and its use in treating RA is well established [ 139 ].…”