Drug Specificity, Synergy and Antagonism in Ultrahigh Capacity Poly(2-oxazoline)/Poly(2-oxazine) based Formulations

Polymer micelles offer the possibility to create a nanoscopic environment that is distinct from the bulk phase. They find applications in catalysis, drug delivery, cleaning, etc. Often, one simply distinguishes between hydrophilic and hydrophobic, but fine-tuning of the microenvironment is possible by adjusting the structure of the polymer amphiphile. Here, we investigated a small library of structurally similar amphiphiles based on poly­(2-oxazoline)­s and poly­(2-oxazine)­s with respect to their solubilization capacity for two extremely water insoluble drugs, curcumin and paclitaxel. We found very significant and orthogonal specificities even if only one methylene group is exchanged between the polymer backbone and side chain. More strikingly, we observed profound synergistic and antagonistic solubilization patterns for the coformulation of the two drugs. Our findings shed new light on host–guest interaction in polymer micelles and such pronounced host–guest specificities in polymer micelles may not only be interesting in drug delivery but also for applications such as micellar catalysis.