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

• Published in: Acta pharmaceutica Sinica. B 2015-11, Vol.5 (6), p.569-576
• Main Authors: Chen, Gui, Hao, Baohua, Ju, Dahong, Liu, Meijie, Zhao, Hongyan, Du, Zhongping, Xia, Jizi
• Format: Article
• Language: English
• Subjects: Collagen-induced arthritis; Micro-electro-mechanical system; Microneedles; Original; Pharmacodynamics; Pharmacokinetics; Triptolide
• ISSN: 2211-3835; 2211-3843
• DOI: 10.1016/j.apsb.2015.09.006

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 onecompartment open model.The relationship equation between plasma concentration and time was C=303.59(e 0.064 t 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.