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Liposome Microencapsulation for the Surface Modification and Improved Entrapment of Cytochrome c for Targeted Delivery

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Title: Liposome Microencapsulation for the Surface Modification and Improved Entrapment of Cytochrome c for Targeted Delivery
Authors: Kajimoto, Kazuaki Browse this author →KAKEN DB
Katsumi, Tatsuhito Browse this author
Nakamura, Takashi Browse this author →KAKEN DB
Kataoka, Masatoshi Browse this author
Harashima, Hideyoshi Browse this author →KAKEN DB
Keywords: Microencapsulation vesicle
Water-in-oil-in-water emulsion
Encapsulation efficiency
Cytochrome c
Issue Date: Jan-2018
Publisher: John Wiley & Sons
Journal Title: Journal of the American Oil Chemists' Society
Volume: 95
Issue: 1
Start Page: 101
End Page: 109
Publisher DOI: 10.1002/aocs.12026
Abstract: In this study, we established a procedure based on the microencapsulation vesicle (MCV) method for preparing surface-modified liposomes, using polyethylene glycol (PEG) and a site-directed ligand, with high entrapment efficiency of cytochrome c (Cyt c). For preparing a water-in-oil (W/O) emulsion, egg phosphatidylcholine and cholesterol were dissolved in organic solvents (O phase) and emulsified by sonication with aqueous solution of Cyt c (W-1). Although the dispersion stability of the W-1/O emulsion was low when n-hexane was used to dissolve the lipids in the O phase, it was substantially improved by using mixed solvents consisting of n-hexane and other organic solvents, such as ethanol and dichloromethane (DCM). The W-1/O emulsion was then added to another water phase (W-2) to prepare the W-1/O/W-2 emulsion. PEG- and/or ligand-modified lipids were introduced into the W-2 phase as external emulsifiers not only for stabilizing the W-1/O/W-2 emulsion but also for modifying the surface of liposomes obtained later. After solvent evaporation and extrusion for downsizing the liposomes, approximately 50% of Cyt c was encapsulated in the liposomes when the mixed solvent consisting of n-hexane and DCM at a volume ratio of 75/25 was used in the O phase. Finally, the fluorescence-labeled liposomes, with a peptide ligand having affinity to the vasculature in adipose tissue, were prepared by the MCV method and intravenously injected into mice. Confocal microscopy showed the substantial accumulation of these liposomes in the adipose tissue vessels. Taken together, the MCV technique, along with solvent optimization, could be useful for generating surface-modified liposomes with high drug entrapment efficiency for targeted delivery.
Rights: This is the peer reviewed version of the following article: Kajimoto, K. , Katsumi, T. , Nakamura, T. , Kataoka, M. and Harashima, H. (2018), Liposome Microencapsulation for the Surface Modification and Improved Entrapment of Cytochrome c for Targeted Delivery. J Am Oil Chem Soc, 95: 101-109. doi:10.1002/aocs.12026, which has been published in final form at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Type: article (author version)
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: 梶本 和昭

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