Pharmacokinetic and pharmacodynamic study of triptolide-loaded liposome hydrogel patch under microneedles on rats with collagen-induced arthritis
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 tri...
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| Format: | Article |
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Elsevier
2015-11-01
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| Series: | Acta Pharmaceutica Sinica B |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383515001380 |
| _version_ | 1819031710265769984 |
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| author | Gui Chen Baohua Hao Dahong Ju Meijie Liu Hongyan Zhao Zhongping Du Jizi Xia |
| author_facet | Gui Chen Baohua Hao Dahong Ju Meijie Liu Hongyan Zhao Zhongping Du Jizi Xia |
| author_sort | Gui Chen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T06:50:22Z |
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| institution | Directory Open Access Journal |
| issn | 2211-3835 2211-3843 |
| language | English |
| last_indexed | 2024-12-21T06:50:22Z |
| publishDate | 2015-11-01 |
| publisher | Elsevier |
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| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-539e3813f59f45d5aa69ec1eae6f3e012022-12-21T19:12:29ZengElsevierActa Pharmaceutica Sinica B2211-38352211-38432015-11-015656957610.1016/j.apsb.2015.09.006Pharmacokinetic and pharmacodynamic study of triptolide-loaded liposome hydrogel patch under microneedles on rats with collagen-induced arthritisGui Chen0Baohua Hao1Dahong Ju2Meijie Liu3Hongyan Zhao4Zhongping Du5Jizi Xia6School of Life and Science, Northwest University, Xi'an 710069, ChinaSchool of Life and Science, Northwest University, Xi'an 710069, ChinaInstitute of Theory, China Academy of Traditional Chinese Medicine, Beijing 100700, ChinaInstitute of Theory, China Academy of Traditional Chinese Medicine, Beijing 100700, ChinaInstitute of Theory, China Academy of Traditional Chinese Medicine, Beijing 100700, ChinaInstitute of Theory, China Academy of Traditional Chinese Medicine, Beijing 100700, ChinaQiannan Institute for Food and Drug Control, Duyun 558000, ChinaTriptolide (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.http://www.sciencedirect.com/science/article/pii/S2211383515001380PharmacokineticsPharmacodynamicsTriptolideMicro-electro-mechanical systemMicroneedlesCollagen-induced arthritis |
| spellingShingle | Gui Chen Baohua Hao Dahong Ju Meijie Liu Hongyan Zhao Zhongping Du Jizi Xia Pharmacokinetic and pharmacodynamic study of triptolide-loaded liposome hydrogel patch under microneedles on rats with collagen-induced arthritis Acta Pharmaceutica Sinica B Pharmacokinetics Pharmacodynamics Triptolide Micro-electro-mechanical system Microneedles Collagen-induced arthritis |
| title | Pharmacokinetic and pharmacodynamic study of triptolide-loaded liposome hydrogel patch under microneedles on rats with collagen-induced arthritis |
| title_full | Pharmacokinetic and pharmacodynamic study of triptolide-loaded liposome hydrogel patch under microneedles on rats with collagen-induced arthritis |
| title_fullStr | Pharmacokinetic and pharmacodynamic study of triptolide-loaded liposome hydrogel patch under microneedles on rats with collagen-induced arthritis |
| title_full_unstemmed | Pharmacokinetic and pharmacodynamic study of triptolide-loaded liposome hydrogel patch under microneedles on rats with collagen-induced arthritis |
| title_short | Pharmacokinetic and pharmacodynamic study of triptolide-loaded liposome hydrogel patch under microneedles on rats with collagen-induced arthritis |
| title_sort | pharmacokinetic and pharmacodynamic study of triptolide loaded liposome hydrogel patch under microneedles on rats with collagen induced arthritis |
| topic | Pharmacokinetics Pharmacodynamics Triptolide Micro-electro-mechanical system Microneedles Collagen-induced arthritis |
| url | http://www.sciencedirect.com/science/article/pii/S2211383515001380 |
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