Amphiphilic Triblock Copolymers from Poly(2-oxazoline) with Different Hydrophobic Blocks: Changes of the Micellar Structures upon Addition of a Strongly Hydrophobic Cancer Drug

Amphiphilic triblock copolymers with poly(2-methyl-2-oxazoline) (MeOx) end blocks and a poly(2-n-butyl-2-oxazoline) (nBuOx) middle block have been found to solubilize large amounts of the cancer drug paclitaxel (PTX) whereas this is not the case when the middle block is more hydrophobic, such as poly(2-n-nonyl-2-oxazoline) (NOx) (Schulz et al., ACS Nano2014, 8, 2686). To further elucidate the origin of this behavior, dilute aqueous solutions (5–10 mg mL⁻¹) of these two copolymers have been investigated by small-angle neutron scattering (SANS), both in the absence and presence of PTX. Whereas PMeOx-b-PNOx-b-PMeOx forms mainly worm-like micelles coexisting with large aggregates, spherical micelles are predominant in PMeOx-b-PnBuOx-b-PMeOx. Already small PTX concentrations lead to shape changes in PMeOx-b-PNOx-b-PMeOx toward spherical micelles. In contrast, changes in the aggregation behavior of PMeOx-b-PnBuOx-b-PMeOx are only observed at higher PTX concentrations with a transformation into raspberry-like particles, which may explain the high PTX loading capacity of PMeOx-b-PnBuOx-b-PMeOx micelles. (Figure presented.) .