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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doaj-889a89047564470e88d14dedf86de1f62020-11-24T22:38:57ZengDove Medical PressInternational Journal of Nanomedicine1178-20132017-08-01Volume 125673568634172Renal-targeted delivery of triptolide by entrapment in pegylated TRX-20-modified liposomesYuan ZJia LLim LYLin JShu GZhao LYe GLiang XJi HFu HZhi-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 cellshttps://www.dovepress.com/renal-targeted-delivery-of-triptolide-by-entrapment-in-pegylated-trx-2-peer-reviewed-article-IJNtriptolidepegylated liposomesTRX-20renal targetingmesangial cells |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yuan Z Jia L Lim LY Lin J Shu G Zhao L Ye G Liang X Ji H Fu H |
spellingShingle |
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 International Journal of Nanomedicine triptolide pegylated liposomes TRX-20 renal targeting mesangial cells |
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 |
series |
International Journal of Nanomedicine |
issn |
1178-2013 |
publishDate |
2017-08-01 |
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 |
topic |
triptolide pegylated liposomes TRX-20 renal targeting mesangial cells |
url |
https://www.dovepress.com/renal-targeted-delivery-of-triptolide-by-entrapment-in-pegylated-trx-2-peer-reviewed-article-IJN |
work_keys_str_mv |
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