Binding of Paclitaxel to Lipid Interfaces: Correlations with Interface Compliance

Abstract

In the present work, we have studied the paclitaxel loading efficiency of lipid bilayers with respect to their compositional behavior, which in turn determines their mechanical properties. We have found that, if a drug with a low water solubility like paclitaxel (or at least a part of this molecule) associates with lipid bilayers, then binding is enhanced if the interface was soft, i.e., highly expandable (low elastic area modulus and tensile strength). We have systematically varied the surface softness of stearoyl oleoyl phosphatidylcholine (SOPC) bilayers by incorporating the lysolipid, monooleoyl phosphatidylcholine (MOPC) to create maximum softness and 50 mol% cholesterol (CHOL) to create less soft, and more stiff membranes, respectively. It was observed that the least soft SOPC bilayers (high elastic area modulus and tensile strength) composed of 50 mol% CHOL, load a negligible amount of paclitaxel (β5µM) in comparison to soft SOPC bilayers made by the incorporation of 28 mol% MOPC, which load 2 mM paclitaxel (12 mol% paclitaxel with respect to total lipid). The paclitaxel loading can be increased to almost 20 mol% for the ultimate in “soft” interfaces, the lysolipid.

Keywords::

• Paclitaxel
• Lysolipid
• Vesicle
• Lipid bilayer
• Micelle