Folded, undulating, and fibrous doxorubicin sulfate crystals in liposomes

High-resolution cryogenic transmission electron microscopy (cryo-TEM) evidenced that doxorubicin sulfate crystals in liposomes (pre-pared 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.(c) 2022 Elsevier Inc. All rights reserved.

Automated summary

High-resolution cryogenic transmission electron microscopy (cryo-TEM) revealed that doxorubicin sulfate crystals in liposomes (prepared by remote loading with ammonium sulfate) formed folded, undulating, and fibrous structures with a diameter of approximately 2.4 nm. An undulating, fibrous crystal considered to be undergrowth, as well as bundles of fibrous crystals, were observed in doxorubicin-loaded liposomes. This explains the formation of various shaped doxorubicin sulfate crystals, such as curved, U-shaped, or circular, in addition to the cylinder and/or rod-like crystals reported in the literature. Liposomes without crystals contained high-density aqueous phases, indicating that doxorubicin is loaded remotely and remains as a solute without precipitation.