Evaluation of glycosylated docetaxel-encapsulated liposomes prepared by remote loading under solubility gradient

Abstract

Docetaxel comprises one of the most effective anti-cancer drugs despite of serious side effects. Liposomes encapsulation is practically feasible to deliver the drug. However, due to the significant hydrophobicity, docetaxel will be integrated into the lipid bilayer resulting in poor encapsulation capacity. Here, we evaluated a remote loading strategy using a solubility gradient made between the two solvents for 7-glucosyloxyacetyldocetaxel, which has enhanced water solubility of docetaxel with a coupled glucose moiety. Therefore, 7-glucosyloxyacetyldocetaxel was more effectively encapsulated into liposomes with 71.0% of encapsulation efficiency than docetaxel. While 7-glucosyloxyacetyldocetaxel exhibited 90.9% of tubulin stabilisation activity of docetaxel, 7-glucosyloxyacetyldocetaxel encapsulated in liposomes significantly inhibited the growth of tumour in vivo with side effects less than unencapsulated drug. Collectively, the encapsulation of 7-glucosyloxyacetyldocetaxel into liposomes by remote loading under the solubility gradient is considered to be a promising application to prepare practical drug delivery system.

Keywords:

• Docetaxel
• glycosylated docetaxel
• liposome
• remote loading method
• solubility gradient

Acknowledgements

The authors appreciate Ms. Mami Asakura for her excellent assistance throughout the entire study.

Disclosure statement

The authors have no conflict of interest associated with this manuscript and the company had no control over the interpretation, writing or publication of this work.

Funding information

This study was partly designed and funded by a commercial company (Ensuiko Sugar Refining Co., Ltd.) and one of the authors, Katsuhiko Mikuni, is an employee of Ensuiko Sugar Refining Co., Ltd. Okayama University, Ensuiko Sugar Refining Co., Ltd. and Hiroki Hamada are the applicants of the Japanese Patent No. 5490326 and the international patent application No. PCT/JP2013/058242 entitled “Method for producing liposome encapsulating paclitaxel monoglycoside and/or docetaxel monoglycoside”. This study was partly supported by Grant-in-Aid for Scientific Research (A) No. 25,2,42045 (MS), Grant-in-Aid for Challenging Exploratory Research No. 26 640079 (MS) and Grant-in-Aid for JSPS Fellows No. 15J08264 (TS) from the Japan Society for the Promotion of Science.