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【論文】崇城大学の小田切先生と田口先生との共同研究成果がJournal of Pharmaceutical Sciencesに採択されました。　(更新 2017.08.08)

Albumin-encapsulated liposomes: A novel drug delivery carrier with hydrophobic drugs encapsulated in the inner aqueous core

Yuko Okamoto a#, Kazuaki Taguchi a#, Keishi Yamasaki a, b, Mina Sakuragi c, Shun’ichi Kuroda d,e, Masaki Otagiri a,b*
a Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan,
b DDS Research Institute, Sojo University, Kumamoto 860-0082 Kumamoto, Japan,
c Department of Nanoscience, Sojo University, Kumamoto 860-0082, Japan,
d The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan,
e Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan

Abstract
Liposomes are clinically used in drug delivery, but loading hydrophobic substances is limited to the hydrophobic space of a lipid membrane, despite the fact that it is favorable to encapsulate substances into the inner aqueous core of liposome, from a drug stability of view. We report herein on the preparation of a liposome with bovine serum albumin encapsulated (BSA-liposome). Using this system, it is possible to encapsulate hydrophobic drugs in the inner aqueous core of the liposome based on the hypothesis that the water solubility of hydrophobic drugs is increased when bound to albumin. The physicochemical properties of the prepared BSA-liposomes could be easily regulated and the loading of hydrophobic drugs in the inner aqueous core of the liposome was dramatically improved by virtue of the drug-binding properties of albumin. An in vivo safety and pharmacokinetic study showed that BSA-liposomes possess favorable properties as a drug carrier, including biocompatibility and a stealth effect. Furthermore, a pharmaceutical study using a hydrophobic drug (tacrolimus)-loaded BSA-liposome in colitis model mice clearly demonstrated the potential of BSA-liposomes as a carrier of a hydrophobic drug (tacrolimus). This new type of hydrophobic drug carrier, an albumin-liposome, has the potential for use in delivering numerous hydrophobic drugs that typically bind to albumin.

Keywords: liposome, albumin, hydrophobic drug, drug-binding, drug delivery

Statement of significance
One of the major obstacles concerning the encapsulation of hydrophobic drugs into the inner aqueous core of a liposome is their low water solubility. To overcome this issue, attempts have been made to modify their chemical structure while retaining the pharmacological effects of such drugs. Attempts to achieve this require comprehensive screening with enormous amounts of time. As a potential solution to this issue, we hypothesized that a hydrophobic substance that binds to albumin could be incorporated into the inner core of a liposome that contained albumin. This strategy takes advantage of an innate characteristic of albumin, namely its drug-binding properties, which would confer water solubility characteristics to a hydrophobic substances. The results reported herein suggest that albumin-liposomes represent a potentially promising and versatile carrier for many types of hydrophobic drugs.