A novel indomethacin/methotrexate/MMP-9 siRNA in situ hydrogel with dual effects of anti-inflammatory activity and reversal of cartilage disruption for the synergistic treatment of rheumatoid arthritis

Abstract

The D/siRNA-NGel was constructed to alleviate pain and swelling, delay the progression of RA, and reverse cartilage and bone disruption.

Chemosensitizing micelles self-assembled from amphiphilic TPGS-indomethacin twin drug for significantly synergetic multidrug resistance reversal

“…The result suggested that TPGS-IDM-NPs-PTX exhibited low synergistic effect for MCF-7 and high synergistic effect for MCF-7/ADR respectively, possibly owing to the stronger chemosensitizing effect of TPGS-IDM on PTX for MCF-7/ADR. Additionally, the micelles could make drugs escape from endosome via proton sponge effect of carboxyl group of IDM,33 once TPGS-IDM was hydrolyzed at endosomal pH/esterase.…”

Biomaterial-based immunotherapeutic strategies for rheumatoid arthritis

“…(2) methotrexate; and (3) siRNA against MMP-9, to halt further damage to the articular ECM. Yin and co-authors administered this hydrogel into the inflamed joint of a CIA mouse and observed significant amelioration of joint pathology as well as a reduction in TNF-α, IL-6, and MMP-9 in serum and in synovial fluid [182]. Remarkably, they also observed joint architecture to return close to baseline [175].…”

“…This scaffold was implanted intra-articularly within the OVA-induced rabbit model and led to amelioration of RA pathology and promoted restoration of cartilage and bone repair [180]. Similarly, Yin et al [182] prepared a hydrogel system with F127 and a polyethyleneimine NP encapsulating (1) the non-steroidal anti-inflammatory drug, indomethacin;…”

Biomimetic and Bioinspired Intervention Strategies for the Treatment of Rheumatoid Arthritis

“…Diverse nanocarriers have been reported to transport methotrexate (MTX) into M1 macrophages (activated). [36][37][38][39][40] To increase the therapeutic effect of MTX for M1 macrophages, various targets for M1 macrophages have been proposed and tested in preclinical studies. These include folic acid (FA) receptors, scavenger receptor class A (SR-A), p65, and Matrix metallopeptidase 9.…”

“…These include folic acid (FA) receptors, scavenger receptor class A (SR-A), p65, and Matrix metallopeptidase 9. [37,38,41,42] Gong et al recently found that palmitic acid-modified bovine serum albumin has a superior targeting capability for SR-A both in vitro and in vivo (Figure 4D). [43] Shi et al proposed a flexible method to target active pro-inflammatory M1 macrophages in RA lesions.…”