Pharmacokinetic and pharmacodynamic study of triptolide-loaded liposome hydrogel patch under microneedles on rats with collagen-induced arthritis

Abstract

Triptolide (TP), a major active component of Tripterygium wilfordii Hook.F. (TWHF), is used to treat rheumatoid arthritis (RA). However, it has a narrow therapeutic window due to its serious toxicities. To increase the therapeutic index, a new triptolide-loaded transdermal delivery system, named triptolide-loaded liposome hydrogel patch (TP-LHP), has been developed. In this paper, we used a micro-needle array to deliver TP-LHP to promote transdermal absorption and evaluated this treatment on the pharmacokinetics and pharmacodynamics of TP-LHP in a rat model of collagen-induced arthritis (CIA). The pharmacokinetic results showed that transdermal delivery of microneedle TP-LHP yielded plasma drug levels which fit a one-compartment open model. The relationship equation between plasma concentration and time was C=303.59×(e−0.064t−e−0.287t). The results of pharmacodynamic study demonstrated that TP-LHP treatment mitigated the degree of joint swelling and suppressed the expressions of fetal liver kinase-1, fetal liver tyrosine kinase-4 and hypoxia-inducible factor-1α in synovium. Other indicators were also reduced by TP-LHP, including hyperfunction of immune, interleukin-1β and interleukin-6 levels in serum. The therapeutic mechanism of TP-LHP might be regulation of the balance between Th1 and Th2, as well as inhibition of the expression and biological effects of vascular endothelial growth factor.

Wogonin ameliorate complete Freund's adjuvant induced rheumatoid arthritis via targeting NF‐κB/MAPK signaling pathway

“…A decrease in GSH could impair the clearance of H2O2 and support OH formation, enhancing the free radical load that leads to homeostasis disturbance . In addition, many trials have shown that there is a lot of oxidative stress in RA patients and this oxidative stress can lead to overproduction of cytokines and harm to the joint tissue . CFA rats have been shown to have reduced antioxidant enzyme activity in the plasma, such as SOD, CAT, and GSH, and some trials have shown that these antioxidant enzymes have RA impacts.…”

“…[30][31][32] In addition, many trials have shown that there is a lot of oxidative stress in RA patients and this oxidative stress can lead to overproduction of cytokines and harm to the joint tissue. 33,34 CFA rats have been shown to have reduced antioxidant enzyme activity in the plasma, such as SOD, CAT, and GSH, and some trials have shown that these antioxidant enzymes have RA impacts. The body therefore has antioxidant enzymatic mechanisms to safeguard tissues from oxidative stress.…”

The triptolide‐induced apoptosis of osteoclast precursor by degradation of cIAP2 and treatment of rheumatoid arthritis of TNF‐transgenic mice

“…(Luo et al, ; Lv et al, ). Various studies had confirmed that TPL as one of the main components of TGV could effectively improve the symptoms of RA through experiments of immunologic adjuvant or collagen‐induced RA mice models (Chen et al, ), but its mechanism was not yet fully clear. This study aimed to investigate whether TPL‐induced apoptosis of OCPs was the key mechanism for the treatment of RA by administering TPL to TNF‐Tg mice whose symptoms are more similar to those in humans with RA and explored its mechanism of induction of OCP apoptosis through in vitro cell experiments.…”

Move to Nano‐Arthrology: Targeted Stimuli‐Responsive Nanomedicines Combat Adaptive Treatment Tolerance (ATT) of Rheumatoid Arthritis

“…To solve this problem, a micro‐needle array was used to delivery triptolide‐loaded liposome hydrogel. The pharmacokinetic results indicated the plasma drug levels fit one‐compartment open model and the pharmacodynamics study showed the treatment mitigated the swelling of the joints and reduced the level of inflammatory factors …”