title: 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.
authors.affiliation: School of Life and Science, Northwest University, Xi'an 710069, China ; Qiannan Institute for Food and Drug Control, Duyun 558000, China.
authors.forename: Gui
authors.initials: G
authors.lastname: Chen
authors.affiliation: School of Life and Science, Northwest University, Xi'an 710069, China.
authors.forename: Baohua
authors.initials: B
authors.lastname: Hao
authors.affiliation: Institute of Theory, China Academy of Traditional Chinese Medicine, Beijing 100700, China.
authors.forename: Dahong
authors.initials: D
authors.lastname: Ju
authors.affiliation: Institute of Theory, China Academy of Traditional Chinese Medicine, Beijing 100700, China.
authors.forename: Meijie
authors.initials: M
authors.lastname: Liu
authors.affiliation: Institute of Theory, China Academy of Traditional Chinese Medicine, Beijing 100700, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Institute of Theory, China Academy of Traditional Chinese Medicine, Beijing 100700, China.
authors.forename: Zhongping
authors.initials: Z
authors.lastname: Du
authors.affiliation: Qiannan Institute for Food and Drug Control, Duyun 558000, China.
authors.forename: Jizi
authors.initials: J
authors.lastname: Xia
keywords: Collagen-induced arthritis; Micro-electro-mechanical system; Microneedles; Pharmacodynamics; Pharmacokinetics; Triptolide