Doubly amphiphilic poly(2-oxazoline)s as high-capacity delivery systems for hydrophobic drugs

Solubilization of highly hydrophobic drugs with carriers that are non-toxic, non-immunogenic and well-defined remains a major obstacle in pharmaceutical sciences. Well-defined amphiphilic di- and triblock copolymers based on poly(2-oxazolines) were prepared and used for the solubilization of Paclitaxel (PTX) and other water-insoluble drugs. Probing the polymer micelles in water with the fluorescence probe pyrene, an unusual high polar microenvironment of the probe was observed. This coincides with an extraordinary large loading capacity for PTX of 45 wt.% active drug in the formulation as well as high water solubility of the resulting formulation. Physicochemical properties of the formulations, ease of preparation and stability upon lyophilization, low toxicity and immunogenicity suggest that poly(2-oxazoline)s are promising candidates for the delivery of highly challenging drugs. Furthermore, we demonstrate that PTX is fully active and provides superior tumor inhibition as compared to the commercial micellar formulation.