Pharmacokinetic and pharmacodynamic study of triptolide-loaded liposome hydrogel patch under microneedles on rats with collagen-induced arthritis.
10.1016/j.apsb.2015.09.006
- Author:
Gui CHEN
1
,
2
;
Baohua HAO
3
;
Dahong JU
4
;
Meijie LIU
4
;
Hongyan ZHAO
4
;
Zhongping DU
4
;
Jizi XIA
5
Author Information
1. School of Life and Science, Northwest University, Xi'an 710069, China
2. Qiannan Institute for Food and Drug Control, Duyun 558000, China.
3. School of Life and Science, Northwest University, Xi'an 710069, China.
4. Institute of Theory, China Academy of Traditional Chinese Medicine, Beijing 100700, China.
5. Qiannan Institute for Food and Drug Control, Duyun 558000, China.
- Publication Type:Journal Article
- Keywords:
Collagen-induced arthritis;
Micro-electro-mechanical system;
Microneedles;
Pharmacodynamics;
Pharmacokinetics;
Triptolide
- From:
Acta Pharmaceutica Sinica B
2015;5(6):569-576
- CountryChina
- Language:English
-
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.
