Preparation and Characterization of Cellulose Ether Liposomes for the Inhibition of Prion Formation in Prion-Infected Cells

被引:8
作者
Nishizawa, Keiko [1 ]
Teruya, Kenta [1 ]
Oguma, Ayumi [1 ]
Sakasegawa, Yuji [1 ]
Schatzl, Hermann [2 ]
Gilch, Sabine [3 ]
Doh-ura, Katsumi [1 ]
机构
[1] Tohoku Univ, Grad Sch Med, Dept Neurochem, Sendai, Miyagi, Japan
[2] Univ Calgary, Dept Comparat Biol & Expt Med, Fac Vet Med, Calgary, AB, Canada
[3] Univ Calgary, Dept Ecosyst & Publ Hlth, Fac Vet Med, Calgary, AB, Canada
基金
日本科学技术振兴机构; 日本学术振兴会;
关键词
bioavailability; cell culture; fluorescence spectroscopy; formulation; liposomes; polymers; polymeric drugs; PROTEIN; DERIVATIVES; MECHANISM; COMPOUND;
D O I
10.1016/j.xphs.2019.03.025
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Prion accumulation in the brain and lymphoreticular system causes fatal neurodegenerative diseases. Our previous study revealed that cellulose ethers (CE) have anti-prion activities in vivo and in prion-infected cells when administered at high doses. This study aims to improve the bioavailability of a representative CE using a liposomal formulation and characterized CE-loaded liposomes in cultured cells. The liposomal formulation reduced the EC50 dose of CE by <1/200-fold in prion-infected cells. Compared to empty liposomes, CE-loaded liposomes were taken up much more highly by prioninfected cells and less by macrophage-like cells. Phosphatidylserine modification reduced the uptake of CE-loaded liposomes in prion-infected cells and did not change the anti-prion activity, whereas increased the uptake in macrophage-like cells. Polyethylene glycol modification reduced the uptake of CE-loaded liposomes in both types of cells and reduced the anti-prion activity in prion-infected cells. These results suggest that a liposomal formulation of CE is more practical than unformulated CE and showed that the CE-loaded liposome uptake levels in prion-infected cells were not associated with anti-prion activity. Although further improvement of the stealth function against phagocytic cells is needed, the liposomal formulation is useful to improve CE efficacy and elucidate the mechanism of CE action. (c) 2019 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
引用
收藏
页码:2814 / 2820
页数:7
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