Folded, undulating, and fibrous doxorubicin sulfate crystals in liposomes

Eiichi Yamamoto; Naoki Hosogi; Yuki Takechi-Haraya; Ken-Ichi Izutsu; Nahoko Uchiyama; Yukihiro Goda

doi:10.1016/j.nano.2022.102631

Folded, undulating, and fibrous doxorubicin sulfate crystals in liposomes

Nanomedicine. 2023 Jan:47:102631. doi: 10.1016/j.nano.2022.102631. Epub 2022 Nov 18.

Authors

Eiichi Yamamoto¹, Naoki Hosogi², Yuki Takechi-Haraya³, Ken-Ichi Izutsu³, Nahoko Uchiyama³, Yukihiro Goda³

Affiliations

¹ National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan. Electronic address: eyamamoto@nihs.go.jp.
² Electron Microscopy Application Department, EM Business Unit, JEOL Ltd, 3-1-2 Musashino Akishima, Tokyo 196-8556, Japan.
³ National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan.

PMID: 36410700
DOI: 10.1016/j.nano.2022.102631

Abstract

High-resolution cryogenic transmission electron microscopy (cryo-TEM) evidenced that doxorubicin sulfate crystals in liposomes (prepared by remote loading with ammonium sulfate) form folded, undulating, and fibrous crystals with a diameter of approximately 2.4 nm. An undulating, fibrous crystal considered to be undergrowth, in addition to bundles of fibrous crystals, was also observed in doxorubicin-loaded liposomes. This explains the validity of the formation of doxorubicin sulfate crystals of various shapes, e.g., curved, U-shaped, or circular, in addition to cylinder and/or rod-like crystals reported in the literature. Liposomes that do not contain crystals have inner aqueous phases with high electron density, suggesting that the doxorubicin is remotely loaded and remains as a solute without precipitation.

Keywords: Doxorubicin sulfate; Equivalency; Liposomes; Morphology; Nanocrystal.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Doxorubicin / pharmacology
Liposomes*
Sulfates*

Substances

Liposomes
Sulfates
Doxorubicin