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Lipids with negative spontaneous curvature decrease the solubility of the cancer drug paclitaxel in liposomes
Victoria Steffes1,2, Scott MacDonald3, John Crowe3
1Materials Department, University of California, Santa Barbara, CA, 93106, USA.
The European Physical Journal. E, Soft Matter
|December 15, 2023
Summary
This study found that lipids 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and glyceryl monooleate (GMO) reduce paclitaxel (PTX) solubility in liposomes. These lipids are unsuitable for developing effective PTX drug carriers.
Area of Science:
- Biochemistry
- Materials Science
- Drug Delivery
Background:
- Paclitaxel (PTX) is a hydrophobic anti-cancer drug requiring effective lipid-based carriers for improved delivery and reduced side effects.
- Lipids like 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and glyceryl monooleate (GMO) are known for membrane fusion properties, utilized in nucleic acid delivery.
- Their potential to enhance PTX delivery via membrane fusion was hypothesized.
Purpose of the Study:
- To evaluate the solubility of paclitaxel (PTX) in cationic liposomes formulated with DOPE or GMO.
- To investigate whether lipid membrane structure or local intermolecular interactions govern PTX solubility.
- To determine the suitability of DOPE and GMO for developing PTX-loaded liposomal drug carriers.
Main Methods:
- Paclitaxel solubility was assessed using time-dependent kinetic phase diagrams and differential-interference-contrast optical microscopy.
- Lipid membrane structure and intermolecular interactions were analyzed using synchrotron small-angle X-ray scattering.
- Lipid formulations were condensed into lipoplex pellets with DNA to enhance X-ray scattering signal.
Main Results:
- Paclitaxel exhibited significantly lower solubility in liposomes containing DOPE or GMO compared to control liposomes (DOTAP/DOPC).
- Notably, PTX showed minimal solubility in GMO-based cationic liposomes.
- Findings indicated that local intermolecular interactions, rather than membrane structure, primarily influenced PTX solubility.
Conclusions:
- Lipids DOPE and GMO, despite their fusogenic properties, are not suitable for formulating liposomal carriers of paclitaxel.
- The negative spontaneous curvature of DOPE and GMO leads to nonlamellar phases that decrease PTX solubility.
- Effective PTX liposomal drug delivery requires careful selection of lipids that promote drug solubility through favorable intermolecular interactions.
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