pH-responsive crosslinked vesicles and micelles based on poly (2-ethyl-2-oxazoline-b-4-vinylpyridine)

Crosslinked vesicles have raised significant interest in the last decade as structures that mimic cells, organelles, and nanoreactors. Herein, the use of 1,4-dibromobutane (DBB) and Cu2+ to crosslink pH-responsive poly(2-ethyl-2-oxazoline-b-4-vinylpyridine) -P(EtOx-b-4VP) -vesicles, or alternatively a vesicles + micelles mixture, whose external layer is composed of the biocompatible and stealth PEtOx is discussed. DBB-crosslinked and Cu2+- crosslinked P(EtOx-b-4VP) aggregates were stable against hydrolytic degradation in the pH range that was studied (2-10) except for Cu2+-crosslinked aggregates at pH = 2. The swelling of the DBB-crosslinked aggregates in an aqueous medium was modulated by the pH-responsiveness of the P4VP block. Freeze-dried DBB-crosslinked aggregates could be dispersed in water and maintained their morphology, which is an advantage for storage and property preservation. Hydrophobic Nile red and Reichardt's dye induced the self-assembly of the non-crosslinked copolymers in an aqueous medium, forming inverse structures with an external layer of P4VP. On the other hand, these hydrophobic molecules were loaded by the crosslinked aggregates even in acidic conditions where both PEtOx and P4VP blocks are swollen by water, and the PEtOx block played an important role in this process. Moreover, the hydrophilic macromolecule rhodamine isothiocyanate-dextran could be encapsulated inside the vesicles. While the external layer of the aggregates composed of PEtOx sorbs hydrophobic molecules, the transport through the polymeric bilayer of the vesicles may be pH-controlled by the P4VP block. Overall, these results indicate that crosslinked P(EtOx-b-4VP) aggregates are feasible candidates in the development of nanoreactors and cell/organelle mimics.