Fabrication of a triptolide-loaded and poly-γ-glutamic acid-based amphiphilic nanoparticle for the treatment of rheumatoid arthritis

Abstract

Triptolide (TP) exhibits immunosuppressive, cartilage-protective and anti-inflammatory effects in rheumatoid arthritis. However, the toxicity of TP limits its widespread use. To decrease the toxic effects, we developed a novel nano-drug carrier system containing TP using poly-γ-glutamic acid-grafted di-tert-butyl L-aspartate hydrochloride (PAT). PAT had an average diameter of 79±18 nm, a narrow polydispersity index (0.18), a strong zeta potential (−32 mV) and a high drug encapsulation efficiency (EE1=48.6%) and loading capacity (EE2=19.2%), and exhibited controlled release (t1/2=29 h). The MTT assay and flow cytometry results indicated that PAT could decrease toxicity and apoptosis induced by free TP on RAW264.7 cells. PAT decreased lipopolysaccharides/interferon γ-induced cytokines expression of macrophage (P<0.05). In vivo, PAT accumulated at inflammatory joints, improved the survival rate and had fewer side effects on tumor necrosis factor α transgenic mice, compared to TP. The blood biochemical indexes revealed that PAT did not cause much damage to the kidney (urea nitrogen and creatinine) and liver (alanine aminotransferase and aspartate aminotransferase). In addition, PAT reduced inflammatory synovial tissue area (P<0.05), cartilage loss (P<0.05), tartrate-resistant acid phosphatase-positive osteoclast area (P<0.05) and bone erosion (P<0.05) in both knee and ankle joints, and showed similar beneficial effect as free TP. In summary, our newly formed nanoparticle, PAT, can reduce the toxicity and guarantee the efficacy of TP, which represents an effective drug candidate for RA with low adverse side effect.

Natural Products for the Treatment of Autoimmune Arthritis: Their Mechanisms of Action, Targeted Delivery, and Interplay with the Host Microbiome

“…with nanoparticle -triptolide showed increased survival rates and significantly reduced liver and kidney toxicity, when compared with free triptolide-treated mice [ 179 ]. In another study, TNF-α transgenic mice treated with nanoparticle-triptolide had a survival rate of 100% and no body weight changes compared to the survival rate of 70% and 20% body weight loss, respectively in mice treated with free triptolide [ 180 ]. However, the difference between the two groups in the bone volume of astragalus (ankle bone) was not significant [ 180 ].…”

Fabrication of a nano polymer wrapping Meg3 ShRNA plasmid for the treatment of cerebral infarction

“…However, the cytotoxicity was an important problem that could not be neglected. PGA was with a large number of anions [37]. MPO was fabricated with the adsorption of cations and anions which could significantly decreased the cytotoxicity induced by cations of PEI.…”

Chronic Inflammatory Diseases, Anti-Inflammatory Agents and Their Delivery Nanosystems

“…The evaluated system of LPS/INFγ-induced cytokine expression of macrophage and in vivo PAT accumulated in inflammatory joints. In addition, PAT reduced inflammatory synovial tissue area, cartilage loss, tartrate-resistant acid phosphatase-resistant osteoclast area, and bone erosion in both the knee and ankle joints and showed a similar beneficial effect as free TP [ 170 ].…”