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

Abstract

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 Nano 2014, 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 wormlike 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 PMeOxb-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 PMeOxb-PnBuOx-b-PMeOx micelles.

More Is Sometimes Less: Curcumin and Paclitaxel Formulations Using Poly(2‐oxazoline) and Poly(2‐oxazine)‐Based Amphiphiles Bearing Linear and Branched C9 Side Chains

“…The apparent R h of A‐pNonOx‐A exhibits a pronounced angle dependence, which could be explained by a broad particle size distribution or non‐spherical aggregates (or both). As it is previously confirmed that formation of worm‐like micelles from A‐pNonOx‐A , it can be assumed that this will be the case here for this new batch. (Figure c; for DLS of non‐annealed A‐pNonOx‐A , see Figure S27b,c, Supporting Information).…”

“…Next, the ABA triblock copolymers comprising pNonOx , pNonOzi , pEtHepOx , and pEtHepOzi as hydrophobic block B as well as pMeOx as hydrophilic blocks A were prepared by consecutive LCROP. As all block copolymers compromise the same hydrophilic blocks A, they will be labeled according to their hydrophobic block A‐pNonOx‐A , A‐pNonOzi‐A , A‐pEtHepOx‐A , and A‐pEtHepOzi‐A .…”

Self-Assembly of Amphiphilic Block Copolypeptoids – Micelles, Worms and Polymersomes

“…Together with the longer circulation of PSR in comparison to PEG, this makes filomicelles from amphiphilic block copolypeptoids interesting candidates in a drug delivery context. However, one must also note and caution that loading of self-assembled polymer based drug delivery systems may have a profound impact on their morphology 60 61 .…”

ABA and BAB Triblock Copolymers Based on 2‐Methyl‐2‐oxazoline and 2‐n‐Propyl‐2‐oxazoline: Synthesis and Thermoresponsive Behavior in Water

“…In contrast to Pluronics, amphiphilic POx have been shown to be able to solubilize unusual large amounts of very hydrophobic molecules . This was found to be sensitive to the polymer composition, in particular, on the choice of the hydrophobic monomer …”