Mixed micelles loaded with the 5-benzylidenethiazolidine-2,4-dione derivative SKLB023 for efficient treatment of non-alcoholic steatohepatitis

Yanping Li,1 Ting Zhang,2 Qinhui Liu,1 Jinhang Zhang,1 Rui Li,1 Shiyun Pu,1 Tong Wu,1 Liang Ma,3 Jinhan He11Laboratory of Clinical Pharmacy and Adverse Drug Reaction; 2Department of Pharmacy; 3Division of Nephrology, Kidney Research Institute, Collaborative Innovation Center of Biotherapy, West Chin...

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Autores principales:	Li Y, Zhang T, Liu Q, Zhang J, Li R, Pu S, Wu T, Ma L, He J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	phosphatidylcholine-bile salt-mixed micelles bioavailability solubilizing efficiency NASH Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/986bea17b640438ea016928130e68381
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spelling	oai:doaj.org-article:986bea17b640438ea016928130e683812021-12-02T07:32:59ZMixed micelles loaded with the 5-benzylidenethiazolidine-2,4-dione derivative SKLB023 for efficient treatment of non-alcoholic steatohepatitis1178-2013https://doaj.org/article/986bea17b640438ea016928130e683812019-05-01T00:00:00Zhttps://www.dovepress.com/mixed-micelles-loaded-with-the-5-benzylidenethiazolidine-24-dione-deri-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yanping Li,1 Ting Zhang,2 Qinhui Liu,1 Jinhang Zhang,1 Rui Li,1 Shiyun Pu,1 Tong Wu,1 Liang Ma,3 Jinhan He11Laboratory of Clinical Pharmacy and Adverse Drug Reaction; 2Department of Pharmacy; 3Division of Nephrology, Kidney Research Institute, Collaborative Innovation Center of Biotherapy, West China Hospital of Sichuan University, Chengdu 610041, People’s Republic of ChinaBackground: SKLB023, a novel 5-benzylidenethiazolidine-2,4-dione based-derivative, specifically inhibits inducible nitric oxide synthase and shows promise for treating non-alcoholic steatohepatitis (NASH). However, its poor water solubility and low bioavailability limits its clinical use. Here the drug was loaded into phosphatidylcholine-bile salt-mixed micelles (PBMM/SKLB023) to overcome these limitations.Methods: PBMM/SKLB023 was developed using a simple co-precipitation method, and formulation parameters were optimized. The pharmacokinetics of PBMM/SKLB023 were investigated in Wistar rats, and therapeutic efficacy was assessed in a mouse model of NASH induced by a diet deficient in methionine- and choline.Results: PBMM/SKLB023 particles were 11.36±2.08 nm based on dynamic light scattering, and loading the drug into micelles improved its water solubility 300-fold. PBMM/SKLB023 inhibited proliferation and activation of HSC-T6 cells more strongly than free SKLB023. PBMM/SKLB023 showed longer mean retention time and higher bioavailability than the free drug after intravenous injection in Wistar rats. In the mouse model of NASH, PBMM/SKLB023 alleviated hepatic lipid accumulation, inflammation, and fibrosis to a significantly greater extent than free SKLB023.Conclusion: PBMM/SKLB023 shows therapeutic potential for treating NASH and liver fibrosis.Keywords: phosphatidylcholine-bile salt-mixed micelles, bioavailability, solubilizing efficiency, NASHLi YZhang TLiu QZhang JLi RPu SWu TMa LHe JDove Medical Pressarticlephosphatidylcholine-bile salt-mixed micellesbioavailabilitysolubilizing efficiencyNASHMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 3943-3953 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	phosphatidylcholine-bile salt-mixed micelles bioavailability solubilizing efficiency NASH Medicine (General) R5-920
spellingShingle	phosphatidylcholine-bile salt-mixed micelles bioavailability solubilizing efficiency NASH Medicine (General) R5-920 Li Y Zhang T Liu Q Zhang J Li R Pu S Wu T Ma L He J Mixed micelles loaded with the 5-benzylidenethiazolidine-2,4-dione derivative SKLB023 for efficient treatment of non-alcoholic steatohepatitis
description	Yanping Li,1 Ting Zhang,2 Qinhui Liu,1 Jinhang Zhang,1 Rui Li,1 Shiyun Pu,1 Tong Wu,1 Liang Ma,3 Jinhan He11Laboratory of Clinical Pharmacy and Adverse Drug Reaction; 2Department of Pharmacy; 3Division of Nephrology, Kidney Research Institute, Collaborative Innovation Center of Biotherapy, West China Hospital of Sichuan University, Chengdu 610041, People’s Republic of ChinaBackground: SKLB023, a novel 5-benzylidenethiazolidine-2,4-dione based-derivative, specifically inhibits inducible nitric oxide synthase and shows promise for treating non-alcoholic steatohepatitis (NASH). However, its poor water solubility and low bioavailability limits its clinical use. Here the drug was loaded into phosphatidylcholine-bile salt-mixed micelles (PBMM/SKLB023) to overcome these limitations.Methods: PBMM/SKLB023 was developed using a simple co-precipitation method, and formulation parameters were optimized. The pharmacokinetics of PBMM/SKLB023 were investigated in Wistar rats, and therapeutic efficacy was assessed in a mouse model of NASH induced by a diet deficient in methionine- and choline.Results: PBMM/SKLB023 particles were 11.36±2.08 nm based on dynamic light scattering, and loading the drug into micelles improved its water solubility 300-fold. PBMM/SKLB023 inhibited proliferation and activation of HSC-T6 cells more strongly than free SKLB023. PBMM/SKLB023 showed longer mean retention time and higher bioavailability than the free drug after intravenous injection in Wistar rats. In the mouse model of NASH, PBMM/SKLB023 alleviated hepatic lipid accumulation, inflammation, and fibrosis to a significantly greater extent than free SKLB023.Conclusion: PBMM/SKLB023 shows therapeutic potential for treating NASH and liver fibrosis.Keywords: phosphatidylcholine-bile salt-mixed micelles, bioavailability, solubilizing efficiency, NASH
format	article
author	Li Y Zhang T Liu Q Zhang J Li R Pu S Wu T Ma L He J
author_facet	Li Y Zhang T Liu Q Zhang J Li R Pu S Wu T Ma L He J
author_sort	Li Y
title	Mixed micelles loaded with the 5-benzylidenethiazolidine-2,4-dione derivative SKLB023 for efficient treatment of non-alcoholic steatohepatitis
title_short	Mixed micelles loaded with the 5-benzylidenethiazolidine-2,4-dione derivative SKLB023 for efficient treatment of non-alcoholic steatohepatitis
title_full	Mixed micelles loaded with the 5-benzylidenethiazolidine-2,4-dione derivative SKLB023 for efficient treatment of non-alcoholic steatohepatitis
title_fullStr	Mixed micelles loaded with the 5-benzylidenethiazolidine-2,4-dione derivative SKLB023 for efficient treatment of non-alcoholic steatohepatitis
title_full_unstemmed	Mixed micelles loaded with the 5-benzylidenethiazolidine-2,4-dione derivative SKLB023 for efficient treatment of non-alcoholic steatohepatitis
title_sort	mixed micelles loaded with the 5-benzylidenethiazolidine-2,4-dione derivative sklb023 for efficient treatment of non-alcoholic steatohepatitis
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/986bea17b640438ea016928130e68381
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Mixed micelles loaded with the 5-benzylidenethiazolidine-2,4-dione derivative SKLB023 for efficient treatment of non-alcoholic steatohepatitis

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