作者
Ruchi Bansal, Jai Prakash, Marieke de Ruijter, Leonie Beljaars, Klaas Poelstra
发表日期
2011/10/3
期刊
Molecular pharmaceutics
卷号
8
期号
5
页码范围
1899-1909
出版商
American Chemical Society
简介
Excessive accumulation of the extracellular matrix proteins primarily produced by activated hepatic stellate cells (HSC) leads to liver fibrosis. To date, no successful therapeutic intervention is available for the treatment of this disease. Platelet derived growth factor beta receptor (PDGFβR) is highly upregulated on disease-inducing activated HSC and thus can be used for delivery of antifibrotic drugs to increase therapeutic efficacy with reduced adverse effects. Interferon gamma (IFNγ) has been recognized as a potent antifibrotic cytokine; however, poor pharmacokinetics and side effects due to frequent administration have limited its clinical use. For HSC-specific delivery, a PDGFβR-specific drug delivery carrier (PPB–HSA) was developed by modifying albumin with PDGFβR-recognizing cyclic peptides. Subsequently, IFNγ was conjugated to PPB–HSA via bifunctional PEG linkers to synthesize PPB–HSA–PEG–IFNγ …
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