Oral Absorption Enhancement of Probucol by PEGylated G5 PAMAM Dendrimer Modified Nanoliposomes

Qian Ma, Yingchun Han, Cong Chen, Yini Cao, Siling Wang, Wenwen Shen, Huayu Zhang, Yanzhi Li, Mallory A. van Dongen, Bing He, Maomao Yu, Lu Xu, Mark M. Banaszak Holl, George Liu, Qiang Zhang, Rong Qi

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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. (Graph Presented).

Original languageEnglish
Pages (from-to)665-674
Number of pages10
JournalMolecular Pharmaceutics
Issue number3
Publication statusPublished - 2 Mar 2015
Externally publishedYes


  • G5-PEG PAMAM dendrimer
  • in vivo pharmacodynamic effects
  • nanoliposome
  • probucol
  • transepithelial absorption and mechanism

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