Nanoscale partitioning of paclitaxel in hybrid lipid-polymer membranes

Paclitaxel is a powerful drug against restenosis and many forms of cancer. However, its clinical application hinges on the ability to achieve suitable stabilized drug concentrations in an aqueous suspension while hindering drug crystallization. To engineer such formulations, it is imperative to understand paclitaxel's partitioning and crystallization within the carrier matrix. Lipid-polymer hybrid films have been recently shown to accommodate large paclitaxel loads and suppress crystallization. Additionally, such hybrid materials promote synergistic drug release compared to the pure constituents. Here, we leverage the composition sensitive photo-Thermal induced resonance (PTIR) technique to study paclitaxel partitioning within hybrid films at the nanoscale. PTIR data reveal that paclitaxel nano-crystals segregate from lipid-only films but are well dispersed in polymer-only films. Remarkably, lipid-polymer hybrid films show enhanced partitioning of paclitaxel at the lipid-polymer phase boundaries, but still stifle crystallization, thus paving the way towards compositional and microstructural engineering of small-drug delivery systems.