Figure 3: Computer simulations on drug–nanoparticle interactions and predictions of drug-loading positions.

(a) Schematic illustration of the SMD simulations. A three-phase model system was constructed to simulate the environment of the drug molecules in a colloidal PLGA–PEG micelle. From the top to bottom the phases are as follows: water (blue); hydrated PEG (grey); and PLGA (green). Different Phe-X (X=CA, C12, OLA and PLGA2k) model drugs (red dot) were steered by a force F (black arrow) progressing along the Z-coordinate to visit all three phases. (b) The molecular structures (in space-filling renderings) of the four Cy7-X analogues. (c) Snapshots of the simulated systems. The Phe-CA compound (orange) is depicted as it moves along the water (left), the PEG (middle) and the PLGA (right) phase. Oxygen atoms (red), PLGA carbons (green), PEG carbon (grey) and water oxygen atoms (cyan). (d,e) Results from the SMD simulations. The forces applied on the Phe-X along the designed pathway (Z-coordinate) are plotted against the position (e), with the different phases indicated by the same colour scheme as in a. The solid lines, meant to guide the eye, are obtained through adjacent-averaging method. The distributions of the force values in each phase are displayed on top of the panels using the same colour code (d). Possible loading positions for each drug model are indicated in the nanoparticle schematics in d.