Renal-targeted delivery of triptolide by entrapment in pegylated TRX-20-modified liposomes

Zhi-xiang Yuan,1,* Lu Jia,2,* Lee Yong Lim,3 Ju-chun Lin,1 Gang Shu,1 Ling Zhao,1 Gang Ye,1 Xiao-xia Liang,1 Hongming Ji,2 Hua-lin Fu1 1Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 2Department of Neurosurgery, Shanxi Provincial People&am...

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Autores principales:	Yuan Z, Jia L, Lim LY, Lin J, Shu G, Zhao L, Ye G, Liang X, Ji H, Fu H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	triptolide pegylated liposomes TRX-20 renal targeting mesangial cells Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/889a89047564470e88d14dedf86de1f6
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spelling	oai:doaj.org-article:889a89047564470e88d14dedf86de1f62021-12-02T01:04:56ZRenal-targeted delivery of triptolide by entrapment in pegylated TRX-20-modified liposomes1178-2013https://doaj.org/article/889a89047564470e88d14dedf86de1f62017-08-01T00:00:00Zhttps://www.dovepress.com/renal-targeted-delivery-of-triptolide-by-entrapment-in-pegylated-trx-2-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Zhi-xiang Yuan,1,* Lu Jia,2,* Lee Yong Lim,3 Ju-chun Lin,1 Gang Shu,1 Ling Zhao,1 Gang Ye,1 Xiao-xia Liang,1 Hongming Ji,2 Hua-lin Fu1 1Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 2Department of Neurosurgery, Shanxi Provincial People’ Hospital, Taiyuan, China; 3Pharmacy, Centre for Optimization of Medicines, School of Allied Health, The University of Western Australia, Crawley, Australia *These authors contributed equally to this work Abstract: Previously, 3,5-dipentadecyloxybenzamidine hydrochloride (TRX-20)-modified liposomes were reported to specifically target mesangial cells (MCs) in glomeruli. To further gain a better understanding of the characteristics and potential application for glomerular diseases of TRX-20-modified liposomes, we synthesized TRX-20 and prepared TRX-20-modified liposomes (TRX-LPs) with different molar ratios – 6% (6%-TRX-LP), 11% (11%-TRX-LP), and 14% (14%-TRX-LP) – of TRX-20 to total lipid in the present study. All TRX-LPs exhibited concentration-dependent toxicity against the MCs at a lipid concentration ranging from 0.01 to 1.0 mg/mL with IC50 values of 3.45, 1.13, and 0.55 mg/mL, respectively. Comparison of the cell viability of TRX-LPs indicated that high levels of TRX-20 caused severe cell mortality, with 11%-TRX-LP showing the higher cytoplasmic accumulation in the MCs. Triptolide (TP) as a model drug was first loaded into 11%-TRX-LP and the liposomes were further modified with PEG5000 (PEG-TRX-TP-LP) in an attempt to prolong their circulation in blood and enhance TP-mediated immune suppression. Due to specific binding to MCs, PEG-TRX-TP-LP undoubtedly showed better anti-inflammatory action in vitro, evidenced by the inhibition of release of nitric oxide (NO) and tumor necrosis factor-α from lipopolysaccharide-stimulated MCs, compared with free TP at the same dose. In vivo, the PEG-TRX-TP-LP effectively attenuated the symptoms of membranous nephropathic (MN) rats and improved biochemical markers including proteinuria, serum cholesterol, and albumin. Therefore, it can be concluded that the TRX-modified liposome is an effective platform to target the delivery of TP to glomeruli for the treatment of MN. Keywords: triptolide, pegylated liposomes, TRX-20, renal targeting, mesangial cellsYuan ZJia LLim LYLin JShu GZhao LYe GLiang XJi HFu HDove Medical Pressarticletriptolidepegylated liposomesTRX-20renal targetingmesangial cellsMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 5673-5686 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	triptolide pegylated liposomes TRX-20 renal targeting mesangial cells Medicine (General) R5-920
spellingShingle	triptolide pegylated liposomes TRX-20 renal targeting mesangial cells Medicine (General) R5-920 Yuan Z Jia L Lim LY Lin J Shu G Zhao L Ye G Liang X Ji H Fu H Renal-targeted delivery of triptolide by entrapment in pegylated TRX-20-modified liposomes
description	Zhi-xiang Yuan,1,* Lu Jia,2,* Lee Yong Lim,3 Ju-chun Lin,1 Gang Shu,1 Ling Zhao,1 Gang Ye,1 Xiao-xia Liang,1 Hongming Ji,2 Hua-lin Fu1 1Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 2Department of Neurosurgery, Shanxi Provincial People’ Hospital, Taiyuan, China; 3Pharmacy, Centre for Optimization of Medicines, School of Allied Health, The University of Western Australia, Crawley, Australia *These authors contributed equally to this work Abstract: Previously, 3,5-dipentadecyloxybenzamidine hydrochloride (TRX-20)-modified liposomes were reported to specifically target mesangial cells (MCs) in glomeruli. To further gain a better understanding of the characteristics and potential application for glomerular diseases of TRX-20-modified liposomes, we synthesized TRX-20 and prepared TRX-20-modified liposomes (TRX-LPs) with different molar ratios – 6% (6%-TRX-LP), 11% (11%-TRX-LP), and 14% (14%-TRX-LP) – of TRX-20 to total lipid in the present study. All TRX-LPs exhibited concentration-dependent toxicity against the MCs at a lipid concentration ranging from 0.01 to 1.0 mg/mL with IC50 values of 3.45, 1.13, and 0.55 mg/mL, respectively. Comparison of the cell viability of TRX-LPs indicated that high levels of TRX-20 caused severe cell mortality, with 11%-TRX-LP showing the higher cytoplasmic accumulation in the MCs. Triptolide (TP) as a model drug was first loaded into 11%-TRX-LP and the liposomes were further modified with PEG5000 (PEG-TRX-TP-LP) in an attempt to prolong their circulation in blood and enhance TP-mediated immune suppression. Due to specific binding to MCs, PEG-TRX-TP-LP undoubtedly showed better anti-inflammatory action in vitro, evidenced by the inhibition of release of nitric oxide (NO) and tumor necrosis factor-α from lipopolysaccharide-stimulated MCs, compared with free TP at the same dose. In vivo, the PEG-TRX-TP-LP effectively attenuated the symptoms of membranous nephropathic (MN) rats and improved biochemical markers including proteinuria, serum cholesterol, and albumin. Therefore, it can be concluded that the TRX-modified liposome is an effective platform to target the delivery of TP to glomeruli for the treatment of MN. Keywords: triptolide, pegylated liposomes, TRX-20, renal targeting, mesangial cells
format	article
author	Yuan Z Jia L Lim LY Lin J Shu G Zhao L Ye G Liang X Ji H Fu H
author_facet	Yuan Z Jia L Lim LY Lin J Shu G Zhao L Ye G Liang X Ji H Fu H
author_sort	Yuan Z
title	Renal-targeted delivery of triptolide by entrapment in pegylated TRX-20-modified liposomes
title_short	Renal-targeted delivery of triptolide by entrapment in pegylated TRX-20-modified liposomes
title_full	Renal-targeted delivery of triptolide by entrapment in pegylated TRX-20-modified liposomes
title_fullStr	Renal-targeted delivery of triptolide by entrapment in pegylated TRX-20-modified liposomes
title_full_unstemmed	Renal-targeted delivery of triptolide by entrapment in pegylated TRX-20-modified liposomes
title_sort	renal-targeted delivery of triptolide by entrapment in pegylated trx-20-modified liposomes
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/889a89047564470e88d14dedf86de1f6
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_version_	1718403329170604032

Renal-targeted delivery of triptolide by entrapment in pegylated TRX-20-modified liposomes

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