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Oral absorption enhancement of probucol by PEGylated G5 PAMAM dendrimer modified nanoliposomes.
Ma, Qian; Han, Yingchun; Chen, Cong; Cao, Yini; Wang, Siling; Shen, Wenwen; Zhang, Huayu; Li, Yanzhi; van Dongen, Mallory A; He, Bing; Yu, Maomao; Xu, Lu; Banaszak Holl, Mark M; Liu, George; Zhang, Qiang; Qi, Rong.
Afiliação
  • Ma Q; Peking University Institute of Cardiovascular Sciences, Peking University Health Science Center, Peking University , Beijing 100191, China.
Mol Pharm ; 12(3): 665-74, 2015 Mar 02.
Article em En | MEDLINE | ID: mdl-25587935
Probucol (PB), an antioxidant drug, is commonly used as a lipid concentration lowering drug to reduce blood plasma cholesterol levels in the clinic. However, the therapeutic effects of this drug are negatively impacted by its poor water solubility and low oral absorption efficiency. In this study, a PEGylated G5 PAMAM dendrimer (G5-PEG) modified nanoliposome was employed to increase water solubility, transepithelial transport, and oral absorption of PB. The uptake mechanism was explored in vitro in Caco-2 cells with the results suggesting that the absorption improvement of G5-PEG modified PB-liposome (PB-liposome/G5-PEG) was related to P-glycoprotein (P-gp) efflux pump but was independent of caveolae endocytosis pathways. Additionally, plasma lipid concentration lowering effects of PB-liposome/G5-PEG were evaluated in vivo in a LDLR-/- hyperlipidemia mouse model. Compared with saline treated group, treatment with PB-liposome/G5-PEG significantly inhibited the increase of plasma total cholesterol (TC) and triglyceride (TG) of mice induced by a high fat diet. Moreover, its lipid concentration lowering effects and plasma drug concentration were greater than PB alone or commercial PB tablets. Our results demonstrated that PB-liposome/G5-PEG significantly increased the oral absorption of PB and therefore significantly improved its pharmacodynamic effects.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Probucol / Sistemas de Liberação de Medicamentos / Nanocápsulas / Lipossomos / Anticolesterolemiantes Limite: Animals / Humans / Male Idioma: En Revista: Mol Pharm Assunto da revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Probucol / Sistemas de Liberação de Medicamentos / Nanocápsulas / Lipossomos / Anticolesterolemiantes Limite: Animals / Humans / Male Idioma: En Revista: Mol Pharm Assunto da revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: China