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Novel lipidated sorbitol-based molecular transporters for non-viral gene delivery

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Title: Novel lipidated sorbitol-based molecular transporters for non-viral gene delivery
Authors: Higashi, Tomoko Browse this author
Khalil, Ikramy A. Browse this author
Maiti, Kaustabh K. Browse this author
Lee, Woo Sirl Browse this author
Akita, Hidetaka Browse this author
Harashima, Hideyoshi Browse this author →KAKEN DB
Chung, Sung-Kee Browse this author
Keywords: Sorbitol
Octaarginine
Guanidine
Condensation
Non-viral gene delivery
MEND
Issue Date: 5-Jun-2009
Publisher: Elsevier B.V.
Journal Title: Journal of Controlled Release
Volume: 136
Issue: 2
Start Page: 140
End Page: 147
Publisher DOI: 10.1016/j.jconrel.2009.01.024
PMID: 19331845
Abstract: In this study, we investigated the possible use of novel lipidated sorbitol-based transporters as functional devices for the improvement of non-viral gene delivery. These transporters are composed of a sorbitol scaffold bearing 8 guanidine moieties that mimic the arginine residues of well-known cell-penetrating peptides. In addition, the transporters carry different lipid groups to aid DNA condensation and facilitate lipid vesicle-binding. We found that the transporters described in this study have the potential to function as plasmid DNA/siRNA-condensers and surface ligands for the enhancement of cellular uptake of lipid vesicles. Shorter lipid chains were found to be better for condensation, whereas longer chains were superior surface ligands. The differential activity of different cores might be explained by facilitated decondensation of cores prepared with transporters comprised of shorter lipid chains. However, we suggest that there is an optimum value of decondensation to achieve higher transfection activities. The proper use of the transporters presented in this study enabled us to prepare a highly efficient non-viral gene delivery system based on a core-shell structure, in which a condensed DNA core is encapsulated by a lipid envelope. A multifunctional envelope-type nano-device prepared with an optimal surface ligand favorably competes with commonly used transfection systems.
Type: article (author version)
URI: http://hdl.handle.net/2115/38732
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: Ikramy A. Khalil

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