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Liposome Microencapsulation for the Surface Modification and Improved Entrapment of Cytochrome c for Targeted Delivery
Author(s) -
Kajimoto Kazuaki,
Katsumi Tatsuhito,
Nakamura Takashi,
Kataoka Masatoshi,
Harashima Hideyoshi
Publication year - 2018
Publication title -
journal of the american oil chemists' society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.512
H-Index - 117
eISSN - 1558-9331
pISSN - 0003-021X
DOI - 10.1002/aocs.12026
Subject(s) - liposome , chemistry , emulsion , polyethylene glycol , sonication , phosphatidylcholine , chromatography , aqueous two phase system , peg ratio , solvent , aqueous solution , organic chemistry , biochemistry , phospholipid , membrane , finance , economics
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.