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

• Published in: Journal of pharmaceutical sciences Vol. 108; no. 8; pp. 2814 - 2820
• Main Authors: Nishizawa, Keiko, Teruya, Kenta, Oguma, Ayumi, Sakasegawa, Yuji, Schätzl, Hermann, Gilch, Sabine, Doh-ura, Katsumi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2019
• Subjects: bioavailability; cell culture; fluorescence spectroscopy; formulation; liposomes; polymeric drugs; polymers; PrPres; CE; PS; liposomes; F-CE; fluorescence spectroscopy; polymeric drugs; R-DHPE; PEG; bioavailability; cell culture; formulation; polymers
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1016/j.xphs.2019.03.025

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 prion-infected 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.