Mesoscale simulation and cryo-TEM of nanoscale drug delivery systems

This work sets out to study the effect of hydrophobic molecules on the morphology of aqueous solutions of amphiphilic block copolymer, which has potential drug delivery applications. The effect is studied both experimentally and by using simulations. Using cryogenic TEM observations, micelles can clearly be visualised and their core size measured. While pure polymer solutions form into spherical micelles with a narrow size distribution, addition of small amounts of hydrophobic drug molecules leads to distortions in shape, a wider size distribution, and larger average core diameter. Simulations are based on a mesoscale dynamic density functional method with Gaussian chain Hamiltonian and mean-field interactions, as implemented in the MesoDyn code. With parameters for the amphiphilic system established in earlier work, and mean-field interactions for the drug molecule derived from structure-property relationships, we obtain good agreement with the TEM observations for the effect of the hydrophobic molecules on the morphology. The simulations clearly show how increasing drug concentration leads to an increase in micelle size, a wider distribution and more elongated rather than spherical micelles.