Parameters determining the hydrolysis rates of poly(2-​oxazoline)​s

Due to the on-going increase of life expectation and the inherent demographic change, the development of easier-to-use and abuse-free dosage forms for active pharmaceutical ingredients (APIs) has become a topic of high interest. Biocompatible polymer networks that are insoluble but swellable in organic solvents, enable the diffusion-mediated loading with various compounds and can therefore act as drug depots.

Advancing our work on poly(2-oxazoline)-based hydrogels with stimuli-induced release of loaded model substrates and hydrogels with optimized attachment to human cancer cells, we here present the next step towards a novel drug dosage form.

For this study, copoly(2-oxazoline)-based polymer networks were crosslinked by thiol-ene click reactions with ether- or ester-functionalized crosslinking units either in-situ during the polymerization or by polymer-analogous reactions. APIs were loaded into the polymer networks by diffusion strategies during a cycle of gel swelling, recovery and drying. Compound release from these networks was correlated with the degree of degradation of the network in alkaline and acidic media as well as by enzymatic hydrolysis of the ester bond (Scheme 1).