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

Keiko Nishizawa, Kenta Teruya, Ayumi Oguma, Yuji Sakasegawa, Hermann Schätzl, Sabine Gilch, Katsumi Doh-ura

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)2814-2820
Number of pages7
JournalJournal of Pharmaceutical Sciences
Volume108
Issue number8
DOIs
Publication statusPublished - 2019 Aug

Keywords

  • bioavailability
  • cell culture
  • fluorescence spectroscopy
  • formulation
  • liposomes
  • polymeric drugs
  • polymers

ASJC Scopus subject areas

  • Pharmaceutical Science

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