Lipids with negative spontaneous curvature decrease the solubility of the cancer drug paclitaxel in liposomes

Area of Science:

• Biochemistry
• Materials Science
• Drug Delivery

Background:

• Paclitaxel (PTX) is a hydrophobic anti-cancer drug requiring effective lipid-based carriers to minimize side effects.
• Lipids such as 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and glyceryl monooleate (GMO) are known for membrane fusion properties, suggesting potential for enhancing drug delivery.

Approach:

• Investigated the solubility of PTX in cationic liposomes formulated with fusogenic lipids (DOPE, GMO) versus non-fusogenic controls (DOTAP, DOPC).
• Utilized time-dependent kinetic phase diagrams and differential-interference-contrast optical microscopy to observe PTX crystallization.
• Employed synchrotron small-angle X-ray scattering to differentiate the roles of lipid membrane structure and local intermolecular interactions on PTX solubility.

Key Points:

• PTX exhibited significantly lower solubility in liposomes containing DOPE and GMO compared to control liposomes.
• GMO-based liposomes showed minimal PTX solubility.
• Fusogenicity of DOPE and GMO is linked to negative spontaneous curvature, promoting nonlamellar phases.

Conclusions:

• Local intermolecular interactions, rather than overall lipid membrane structure or fusogenicity, predominantly govern PTX solubility.
• DOPE and GMO are unsuitable components for developing effective lipid carriers for paclitaxel delivery due to poor drug solubility.