Nanomorphology tuning in doxorubicin-loaded liposomes via cooling-induced doxorubicin-crystallization and membrane phase transition

Abstract

Rational control of doxorubicin (DOX)-loaded liposome morphology was achieved by changing the cooling rate without altering the composition. Slow cooling produced prolate liposomes containing a linear DOX-sulfate fiber-bundle, whereas rapid freezing gave nearly spherical liposomes with a curved DOX-sulfate fiber-bundle. In situ SAXS and ¹H NMR measurements revealed that the morphological differences were determined by the sequence of DOX-sulfate fiber-bundle formation and stiffness increase of the lipid membrane, depending on the cooling rate.