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

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• 作者：Gui Chen^a ; ^c ; Baohua Hao^a ; ^{haobaohua211@126.com" class="auth_mail" title="E-mail the corresponding author} ; Dahong Ju^b ; Meijie Liu^b ; Hongyan Zhao^b ; Zhongping Du^b ; Jizi Xia^c
• 关键词：Pharmacokinetics ; Pharmacodynamics ; Triptolide ; Micro-electro-mechanical system ; Microneedles ; Collagen-induced arthritis
• 刊名：Acta Pharmaceutica Sinica B
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：5
• 期：6
• 页码：569-576
• 全文大小：1781 K

文摘

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.