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Article: Celastrol-loaded lactosylated albumin nanoparticles attenuate hepatic steatosis in non-alcoholic fatty liver disease

TitleCelastrol-loaded lactosylated albumin nanoparticles attenuate hepatic steatosis in non-alcoholic fatty liver disease
Authors
Issue Date2022
Citation
Journal of Controlled Release, 2022, v. 347, p. 44-54 How to Cite?
AbstractNon-alcoholic fatty liver disease (NAFLD) is a multifactorial disease with several liver-associated pathologic characteristics such as aberrant lipid accumulation, persistent chronic inflammation and hyperactive endoplasmic reticulum (ER) stress. Plant-derived celastrol (CEL) appeared to be a promising anti-inflammatory and anti-obesity drug but the clinical application was delayed by low oral bioavailability. The present study was designed for developing biodegradable albumin-based nanoparticles to deliver CEL to the liver for treating NAFLD. CEL was entrapped into lactosylated bovine serum albumin (Lac-BSA) by high pressure homogenization to generate CEL-loaded Lac-BSA nanoparticles (CEL-Lac-BSA). CEL-Lac-BSA displayed spherical morphology, narrow size distribution at 158.6 ± 3.4 nm and reasonable drug-loading efficiency at 13.62 ± 0.13%. CEL-Lac-BSA not only showed better hepatocyte uptake and hepatic deposition than free CEL, but also outperformed in reducing lipid deposition, ameliorating liver function and enhancing insulin sensitivity in a mouse model of diet-induced NAFLD. Mechanistic studies indicated that CEL-Lac-BSA more effectively downregulated the mRNA levels of genes for lipogenesis and lipid transporter while upregulated the mRNA levels of lipolysis mediators. Western blot analysis confirmed the outperformance of CEL-Lac-BSA in enhancing the activation of AMP-activated protein kinase (AMPK) and silent information regulation 2 homolog (SIRT1) and the protein levels of fatty acid synthase (FASN) and sterol regulatory element-binding protein-1c (SREBP1c) in NAFLD mice. Taken together, CEL-Lac-BSA showed better potential in the treatment of diet-induced NAFLD. Lactose-coating of albumin-based nanoparticles effectively facilitated the liver-targeting release of hydrophobic drug CEL for ameliorating hepatic steatosis. Therefore, CEL-Lac-BSA may be translated into a potential clinical therapy against obesity and NAFLD.
Persistent Identifierhttp://hdl.handle.net/10722/313798
ISSN
2023 Impact Factor: 10.5
2023 SCImago Journal Rankings: 2.157
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorFAN, N-
dc.contributor.authorZhao, J-
dc.contributor.authorZhao, W-
dc.contributor.authorZHANG, X-
dc.contributor.authorSONG, Q-
dc.contributor.authorSHEN, Y-
dc.contributor.authorShum, HC-
dc.contributor.authorWang, Y-
dc.contributor.authorRong, J-
dc.date.accessioned2022-07-05T05:05:55Z-
dc.date.available2022-07-05T05:05:55Z-
dc.date.issued2022-
dc.identifier.citationJournal of Controlled Release, 2022, v. 347, p. 44-54-
dc.identifier.issn0168-3659-
dc.identifier.issn0168-3659-
dc.identifier.urihttp://hdl.handle.net/10722/313798-
dc.description.abstractNon-alcoholic fatty liver disease (NAFLD) is a multifactorial disease with several liver-associated pathologic characteristics such as aberrant lipid accumulation, persistent chronic inflammation and hyperactive endoplasmic reticulum (ER) stress. Plant-derived celastrol (CEL) appeared to be a promising anti-inflammatory and anti-obesity drug but the clinical application was delayed by low oral bioavailability. The present study was designed for developing biodegradable albumin-based nanoparticles to deliver CEL to the liver for treating NAFLD. CEL was entrapped into lactosylated bovine serum albumin (Lac-BSA) by high pressure homogenization to generate CEL-loaded Lac-BSA nanoparticles (CEL-Lac-BSA). CEL-Lac-BSA displayed spherical morphology, narrow size distribution at 158.6 ± 3.4 nm and reasonable drug-loading efficiency at 13.62 ± 0.13%. CEL-Lac-BSA not only showed better hepatocyte uptake and hepatic deposition than free CEL, but also outperformed in reducing lipid deposition, ameliorating liver function and enhancing insulin sensitivity in a mouse model of diet-induced NAFLD. Mechanistic studies indicated that CEL-Lac-BSA more effectively downregulated the mRNA levels of genes for lipogenesis and lipid transporter while upregulated the mRNA levels of lipolysis mediators. Western blot analysis confirmed the outperformance of CEL-Lac-BSA in enhancing the activation of AMP-activated protein kinase (AMPK) and silent information regulation 2 homolog (SIRT1) and the protein levels of fatty acid synthase (FASN) and sterol regulatory element-binding protein-1c (SREBP1c) in NAFLD mice. Taken together, CEL-Lac-BSA showed better potential in the treatment of diet-induced NAFLD. Lactose-coating of albumin-based nanoparticles effectively facilitated the liver-targeting release of hydrophobic drug CEL for ameliorating hepatic steatosis. Therefore, CEL-Lac-BSA may be translated into a potential clinical therapy against obesity and NAFLD.-
dc.languageeng-
dc.relation.ispartofJournal of Controlled Release-
dc.titleCelastrol-loaded lactosylated albumin nanoparticles attenuate hepatic steatosis in non-alcoholic fatty liver disease-
dc.typeArticle-
dc.identifier.emailZhao, J: zhaojia7@hku.hk-
dc.identifier.emailShum, HC: ashum@hku.hk-
dc.identifier.emailWang, Y: yuwanghk@hku.hk-
dc.identifier.emailRong, J: jrong@hku.hk-
dc.identifier.authorityShum, HC=rp01439-
dc.identifier.authorityWang, Y=rp00239-
dc.identifier.authorityRong, J=rp00515-
dc.identifier.doi10.1016/j.jconrel.2022.04.034-
dc.identifier.pmid35483638-
dc.identifier.scopuseid_2-s2.0-85129363987-
dc.identifier.hkuros333967-
dc.identifier.volume347-
dc.identifier.spage44-
dc.identifier.epage54-
dc.identifier.isiWOS:000802915000004-

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