title: Membrane Microdomain Structures of Liposomes and Their Contribution to the Cellular Uptake Efficiency into HeLa Cells.
abstract: The purpose of this study is to obtain a comprehensive relationship between membrane microdomain structures of liposomes and their cellular uptake efficiency. Model liposomes consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/cholesterol (Ch) were prepared with various lipid compositions. To detect distinct membrane microdomains in the liposomes, fluorescence-quenching assays were performed at temperatures ranging from 25 to 60 °C using 1,6-diphenyl-1,3,5-hexatriene-labeled liposomes and (2,2,6,6-tetramethylpiperidin-1-yl)oxyl. From the data analysis using the response surface method, we gained a better understanding of the conditions for forming distinct domains (Lo, Ld, and gel phase membranes) as a function of lipid composition. We further performed self-organizing maps (SOM) clustering to simplify the complicated behavior of the domain formation to obtain its essence. As a result, DPPC/DOPC/Ch liposomes in any lipid composition were integrated into five distinct clusters in terms of similarity of the domain structure. In addition, the findings from synchrotron small-angle X-ray scattering analysis offered further insight into the domain structures. As a last phase of this study, an in vitro cellular uptake study using HeLa cells was conducted using SOM clusters' liposomes with/without PEGylation. As a consequence of this study, higher cellular uptake was observed from liposomes having Ch-rich ordered domains.
authors.affiliation: Department of Pharmaceutical Technology, Graduate School of Medical and Pharmaceutical Science, Unversity of Toyama , Sugitani 2630, Toyama-shi, Toyama 930-0194, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Onuki
authors.affiliation: Department of Pharmaceutics and §Department of Drug Delivery Research, Hoshi University , Ebara 2-4-41, Shinagawa, Tokyo 142-8501, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Obata
authors.forename: Kumi
authors.initials: K
authors.lastname: Kawano
authors.affiliation: Department of Pharmaceutics and §Department of Drug Delivery Research, Hoshi University , Ebara 2-4-41, Shinagawa, Tokyo 142-8501, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Sano
authors.affiliation: Department of Pharmaceutics and §Department of Drug Delivery Research, Hoshi University , Ebara 2-4-41, Shinagawa, Tokyo 142-8501, Japan.
authors.forename: Reina
authors.initials: R
authors.lastname: Matsumoto
authors.affiliation: Department of Pharmaceutical Technology, Graduate School of Medical and Pharmaceutical Science, Unversity of Toyama , Sugitani 2630, Toyama-shi, Toyama 930-0194, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Department of Pharmaceutics and §Department of Drug Delivery Research, Hoshi University , Ebara 2-4-41, Shinagawa, Tokyo 142-8501, Japan.
authors.forename: Kozo
authors.initials: K
authors.lastname: Takayama
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000031:analogs & derivatives* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry*; D021962:Membrane Microdomains / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000378:metabolism*; D013696:Temperature
chemical_list: D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D015060:1,2-Dipalmitoylphosphatidylcholine; C081581:colfosceril palmitate; D002784:Cholesterol; C017251:1,2-oleoylphosphatidylcholine
keywords: Kohonen’s self-organizing maps; cellular uptake efficiency; liposome; membrane microdomain; response surface method