title: G5 PAMAM dendrimer versus liposome: a comparison study on the in vitro transepithelial transport and in vivo oral absorption of simvastatin.
abstract: This study compared formulation effects of a dendrimer and a liposome preparation on the water solubility, transepithelial transport, and oral bioavailability of simvastatin (SMV). Amine-terminated G5 PAMAM dendrimer (G5-NH2) was chosen to form SMV/G5-NH2 molecular complexes, and SMV-liposomes were prepared by using a thin film dispersion method. The effects of these preparations on the transepithelial transport were investigated in vitro using Caco-2 cell monolayers. Results indicated that the solubility and transepithelial transport of SMV were significantly improved by both formulations. Pharmacokinetic studies in rats also revealed that both the SMV/G5-NH2 molecular complexes and the SMV-liposomes significantly improved the oral bioavailability of SMV with the liposomes being more effective than the G5-NH2. The overall better oral absorption of SMV-liposomes as compared to SMV/G5-NH2 molecular complexes appeared to arise from better liposomal solubilization and encapsulation of SMV and more efficient intracellular SMV delivery.
  
  
  BACKGROUND
  Various carrier systems have been designed to enhance drug delivery via the oral route. In this study, the authors compared G5 PAMAM dendrimers to liposome preparations in terms of solubility, transepithelial transport, and oral bioavailability of this poorly water-soluble drug. This understanding has improved our knowledge in the further development of drug carrier systems.
authors: Peking University Institute of Cardiovascular Sciences, Peking University, Beijing, China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, China. Electronic address: ronaqi@bjmu.edu.cn.
authors: Rong
authors: R
authors: Qi
authors: Peking University Institute of Cardiovascular Sciences, Peking University, Beijing, China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, China; School of Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, China.
authors: Heran
authors: H
authors: Zhang
authors: Peking University Institute of Cardiovascular Sciences, Peking University, Beijing, China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, China.
authors: Lu
authors: L
authors: Xu
authors: Peking University Institute of Cardiovascular Sciences, Peking University, Beijing, China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, China.
authors: Wenwen
authors: W
authors: Shen
authors: Peking University Institute of Cardiovascular Sciences, Peking University, Beijing, China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, China.
authors: Cong
authors: C
authors: Chen
authors: Peking University Institute of Cardiovascular Sciences, Peking University, Beijing, China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, China.
authors: Chao
authors: C
authors: Wang
authors: Peking University Institute of Cardiovascular Sciences, Peking University, Beijing, China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, China.
authors: Yini
authors: Y
authors: Cao
authors: Peking University Institute of Cardiovascular Sciences, Peking University, Beijing, China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, China.
authors: Yunan
authors: Y
authors: Wang
authors: Department of Chemistry, University of Michigan, Ann Arbor, MI, USA.
authors: Mallory A
authors: MA
authors: van Dongen
authors: School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors: Bing
authors: B
authors: He
authors: School of Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, China.
authors: Siling
authors: S
authors: Wang
authors: Peking University Institute of Cardiovascular Sciences, Peking University, Beijing, China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, China.
authors: George
authors: G
authors: Liu
authors: Department of Chemistry, University of Michigan, Ann Arbor, MI, USA.
authors: Mark M
authors: MM
authors: Banaszak Holl
authors: School of Pharmaceutical Sciences, Peking University, Beijing, China. Electronic address: zqdodo@bjmu.edu.cn.
authors: Qiang
authors: Q
authors: Zhang
mesh_terms: D000284:Administration, Oral; D000586:Amination; D000818:Animals; D001692:Biological Transport; D018938:Caco-2 Cells; D050091:Dendrimers / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008081:Liposomes; D008297:Male; D062793:Occludin / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D012995:Solubility
chemical_list: D050091:Dendrimers; D004337:Drug Carriers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008081:Liposomes; D062793:Occludin; C104700:PAMAM Starburst; D034741:RNA, Small Interfering; D019821:Simvastatin
keywords: G5-NH(2) PAMAM dendrimer; Liposome; Oral bioavailability; Simvastatin; Transepithelial transport