Long-Circulating and Fusogenic Liposomes Loaded with Paclitaxel and Doxorubicin: Effect of Excipient, Freezing, and Freeze-Drying on Quality Attributes.

Abstract

LCFL-PTX/DXR was evaluated by freeze-drying microscopy (glass transition, Tg'), differential scanning calorimetry (collapse temperature, Tc), freeze-thawing and freeze-drying processes. Freeze-dried samples were evaluated by thermogravimetry (residual moisture) and the resuspended liposomes were characterized in terms of size, polydispersity index (PI), zeta potential (ZP), and drug content. Liposomes morphology was evaluated by cryomicroscopy. Trehalose protected PTX cargo upon freeze-thawing and more than 80% of the original DXR retention. The formulations with trehalose resulted in a cake with 5-7% of moisture content (200-240 nm); 44-60% of PTX retention, and 25-35% of DXR retention, with the variations caused by cryoprotector concentration and process changes. Trehalose protected liposome integrity, maintaining PTX retention and most of DXR upon freeze-thawing. Freeze-drying reduced the retention of both drugs inside all liposomes, whereas formulation with trehalose presented minor losses. Therefore, this frozen formulation is an alternative product option, with no need for manipulation before use.