| Title | G5-PEG PAMAM dendrimer incorporating nanostructured lipid carriers enhance oral bioavailability and plasma lipid-lowering effect of probucol |
| Authors | Qi, Rong Li, Yan-zhi Chen, Cong Cao, Yi-ni Yu, Mao-mao Xu, Lu He, Bing Jie, Xu Shen, Wen-wen Wang, Yu-nan van Dongen, Mallory A. Liu, Guo-qing Holl, Mark M. Banaszak Zhang, Qiang Ke, Xue |
| Affiliation | Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100191, Peoples R China. Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing, Peoples R China. Peking Univ, Sch Pharmaceut Sci, Beijing 100191, Peoples R China. China Pharmaceut Univ, Sch Pharm, Nanjing 210009, Jiangsu, Peoples R China. Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA. Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, 38 Xueyuan Rd, Beijing 100191, Peoples R China. |
| Keywords | PEG-PAMAM dendrimers Nanostructured lipid carriers Probucol Water solubility Oral bioavailability Lipid-lowering effect SYSTEMS CHI-ADDNSS DRUG-DELIVERY HYPERCHOLESTEROLEMIA TECHNOLOGY ABSORPTION LIPOSOMES TRANSPORT POLYMERS RELEASE MICE |
| Issue Date | 2015 |
| Publisher | JOURNAL OF CONTROLLED RELEASE |
| Citation | JOURNAL OF CONTROLLED RELEASE.2015,210,160-168. |
| Abstract | This work aimed to improve the oral bioavailability and plasma lipid-lowering effect of probucol (PB) by constructing a combined drug delivery system (CDDS) composed of nanostructured lipid carrier (NLC) and PEGylated poly(amidoamine) dendrimer (PEG-PAMAM). PEG-PAMAM with dendrimer generations of 5 (G5PEG) or 7 (G7-PEG) were incorporated in PB-NLCs to form PB-CDDSs, PB-NLCs/G5-PEG and PB-NLCs/G7-PEG. The resultant two kinds of PB-CDDSs were characterized by particle size, zeta potential, drug encapsulation efficacy, PB release rates, and physical stability. Formulation effects of NLC and CDDS on the cellular uptake of hydrophobic drug were explored in Caco-2 cells by fluorescent Cy5 dye as a hydrophobic drug model. Furthermore, in vivo pharmacokinetics of the PB-CDDS composed of G5-PEG and PB-NLCs were investigated in a low density lipoprotein receptor knockout (LDLr-/-) mouse model, including plateau plasma PB concentrations after oral administration of multiple doses, and bioavailability after oral administration of a single dose of different PB formulations. In addition, lipid-lowering effect of PB-NLCs/G5-PEG was studied. The results indicate that both G5-PEG and G7-PEG significantly improved aqueous solubility of PB. The two PB-CDDSs exhibited similar particle size (around 150 nm) as PB-NLCs, but slower PB burst release rate, higher total PB release amount, and better particle morphology and storage stability than PB-NLCs. In comparison with traditional NLC, CDDS dramatically enhanced cellular uptake of Cy5 into Caco-2 cells. In vivo results demonstrate that PB-NLCs/G5-PEG had the highest plateau plasma PB concentration and oral bioavailability, and the greatest cholesterollowering effect in comparison with PB suspensions and PB-NLCs. Therefore, G5-PEG incorporating NLC can be exploited as a promising drug delivery system to improve oral bioavailability and lipid-lowering effect of PB. (C) 2015 Elsevier B.V. All rights reserved. |
| URI | http://hdl.handle.net/20.500.11897/418085 |
| ISSN | 0168-3659 |
| DOI | 10.1016/j.jconrel.2015.05.281 |
| Indexed | SCI(E) EI PubMed |
| Appears in Collections: | 药学院 |
