Fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo

Li Zhang,1,2 Tengteng Wang,1,2 Qiang Li,1,2 Jing Huang,3 Hao Xu,1,2 Jinlong Li,1,2 Yongjun Wang,1,2 Qianqian Liang1,21Department of Orthopaedics, Longhua Hospital, 2Institute of Spine, Shanghai University of Traditional Chinese Medicine, 3Biochemistry and Molecular Biology, School of Life Science, E...

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Autores principales:	Zhang L, Wang TT, Li Q, Huang J, Xu H, Li JL, Wang YJ, Liang QQ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Triptolide toxicity γ-poly-γ-glutamic acid drug carrier system Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/7061b7866c9f41b88590075cd7400580
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spelling	oai:doaj.org-article:7061b7866c9f41b88590075cd74005802021-12-02T02:32:07ZFabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo1178-2013https://doaj.org/article/7061b7866c9f41b88590075cd74005802016-06-01T00:00:00Zhttps://www.dovepress.com/fabrication-of-novel-vesicles-of-triptolide-for-antirheumatoid-activit-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Li Zhang,1,2 Tengteng Wang,1,2 Qiang Li,1,2 Jing Huang,3 Hao Xu,1,2 Jinlong Li,1,2 Yongjun Wang,1,2 Qianqian Liang1,21Department of Orthopaedics, Longhua Hospital, 2Institute of Spine, Shanghai University of Traditional Chinese Medicine, 3Biochemistry and Molecular Biology, School of Life Science, East China Normal University, Shanghai, People’s Republic of China Abstract: Triptolide (TP) displays a strong immunosuppression function in immune-mediated diseases, especially in the treatment of rheumatoid arthritis. However, in addition to its medical and health-related functions, TP also exhibits diverse pharmacological side effects, for instance, liver and kidney toxicity and myelosuppression. In order to reduce the side effects, a nano drug carrier system (γ-PGA-l-PAE-TP [PPT]), in which TP was loaded by a poly-γ-glutamic acid-grafted l-phenylalanine ethylester copolymer, was developed. PPT was characterized by photon scattering correlation spectroscopy and transmission electron microscopy, which demonstrated that the average diameter of the drug carrier system is 98±15 nm, the polydispersity index is 0.18, the zeta potential is –35 mV, and the TP encapsulation efficiency is 48.6% with a controlled release manner. The methylthiazolyldiphenyl-tetrazolium bromide assay and flow cytometry revealed that PPT could decrease toxicity and apoptosis induced by free TP on RAW264.7 cells, respectively. The detection of reactive oxygen species showed that PPT could decrease the cellular reactive oxygen species induced by TP. Compared with the free TP-treated group, PPT improved the survival rate of the mice (P<0.01) and had no side effects or toxic effects on the thymus index (P>0.05) and spleen index (P>0.05). The blood biochemical indexes revealed that PPT did not cause much damage to the kidney (blood urea nitrogen and creatinine), liver (serum alanine aminotransferase and aspartate aminotransferase), or blood cells (P>0.05). Meanwhile, hematoxylin and eosin staining and terminal-deoxynucleotidyl transferase dUTP nick-end labeling staining indicated that PPT reduced the damage of free TP on the liver, kidney, and spleen. Our results demonstrated that PPT reduced free TP toxicity in vitro and in vivo and that it is a promising fundamental drug delivery system for rheumatoid arthritis treatment. Keywords: triptolide, toxicity, poly-γ-glutamic acid, drug carrier systemZhang LWang TTLi QHuang JXu HLi JLWang YJLiang QQDove Medical PressarticleTriptolidetoxicityγ-poly-γ-glutamic aciddrug carrier systemMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 2663-2673 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Triptolide toxicity γ-poly-γ-glutamic acid drug carrier system Medicine (General) R5-920
spellingShingle	Triptolide toxicity γ-poly-γ-glutamic acid drug carrier system Medicine (General) R5-920 Zhang L Wang TT Li Q Huang J Xu H Li JL Wang YJ Liang QQ Fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo
description	Li Zhang,1,2 Tengteng Wang,1,2 Qiang Li,1,2 Jing Huang,3 Hao Xu,1,2 Jinlong Li,1,2 Yongjun Wang,1,2 Qianqian Liang1,21Department of Orthopaedics, Longhua Hospital, 2Institute of Spine, Shanghai University of Traditional Chinese Medicine, 3Biochemistry and Molecular Biology, School of Life Science, East China Normal University, Shanghai, People’s Republic of China Abstract: Triptolide (TP) displays a strong immunosuppression function in immune-mediated diseases, especially in the treatment of rheumatoid arthritis. However, in addition to its medical and health-related functions, TP also exhibits diverse pharmacological side effects, for instance, liver and kidney toxicity and myelosuppression. In order to reduce the side effects, a nano drug carrier system (γ-PGA-l-PAE-TP [PPT]), in which TP was loaded by a poly-γ-glutamic acid-grafted l-phenylalanine ethylester copolymer, was developed. PPT was characterized by photon scattering correlation spectroscopy and transmission electron microscopy, which demonstrated that the average diameter of the drug carrier system is 98±15 nm, the polydispersity index is 0.18, the zeta potential is –35 mV, and the TP encapsulation efficiency is 48.6% with a controlled release manner. The methylthiazolyldiphenyl-tetrazolium bromide assay and flow cytometry revealed that PPT could decrease toxicity and apoptosis induced by free TP on RAW264.7 cells, respectively. The detection of reactive oxygen species showed that PPT could decrease the cellular reactive oxygen species induced by TP. Compared with the free TP-treated group, PPT improved the survival rate of the mice (P<0.01) and had no side effects or toxic effects on the thymus index (P>0.05) and spleen index (P>0.05). The blood biochemical indexes revealed that PPT did not cause much damage to the kidney (blood urea nitrogen and creatinine), liver (serum alanine aminotransferase and aspartate aminotransferase), or blood cells (P>0.05). Meanwhile, hematoxylin and eosin staining and terminal-deoxynucleotidyl transferase dUTP nick-end labeling staining indicated that PPT reduced the damage of free TP on the liver, kidney, and spleen. Our results demonstrated that PPT reduced free TP toxicity in vitro and in vivo and that it is a promising fundamental drug delivery system for rheumatoid arthritis treatment. Keywords: triptolide, toxicity, poly-γ-glutamic acid, drug carrier system
format	article
author	Zhang L Wang TT Li Q Huang J Xu H Li JL Wang YJ Liang QQ
author_facet	Zhang L Wang TT Li Q Huang J Xu H Li JL Wang YJ Liang QQ
author_sort	Zhang L
title	Fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo
title_short	Fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo
title_full	Fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo
title_fullStr	Fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo
title_full_unstemmed	Fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo
title_sort	fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/7061b7866c9f41b88590075cd7400580
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Fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo

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