Computational studies on self-assembled paclitaxel structures: Templates for hierarchical block copolymer assemblies and sustained drug release

Paclitaxel-loaded poly(ethylene oxide)-b-poly(lactide) (PEO-b-PLA) systems have been observed to assemble into fiber structures with remarkably different properties using different chirality and molecular weight of PLA segments. In this study, dissipative particle dynamics (DPD) simulations were carried out to elaborate the microstructures and properties of pure paclitaxel and paclitaxel-loaded PEO-b-PLA systems. Paclitaxel molecules formed ribbon or fiber like structures in water. With the addition of PEO-b-PDLA, PEO-b-PLLA and their stereocomplex, paclitaxel acted as a template and polymer molecules assembled around the paclitaxel structure to form core/shell structured fibers having a PEO shell. For PEO19-b-PDLA27 and PEO19-b-PLLA27 systems, PLA segments and paclitaxel molecules were distributed homogeneously in the core of fibers based on the hydrophobic interactions. In the stereocomplex formulation, paclitaxel molecules were more concentrated in the inner PLA stereocomplex core, which led to slower release of paclitaxel. By increasing the length of PLA segments (e.g. 8,16,22 and 27), the crystalline structure of paclitaxel was gradually weakened and destroyed, which was further proved by X-ray diffraction studies. All the simulation results agreed well with experimental data, suggesting that the DPD simulations may provide a powerful tool for designing drug delivery systems.