Cytotoxicity and Bioimmunological Activity of Poly(2-Isopropenyl-2-oxazoline) Conjugates with Ibuprofen Using 3D Reconstructed Tissue Models

Poly­(2-isopropenyl-2-oxazoline) (PIPOx) represents a universal polymer platform with pendant 2-oxazoline groups, allowing the preparation of biomaterials for various biomedical applications. However, there is a lack of information on PIPOx concerning the effect of molar mass (M n) on cytotoxicity and bioimmunological properties. Here, aqueous copper(0)-mediated reversible-deactivation radical polymerization (Cu0-RDPR) was used for the preparation of PIPOx with defined M n and low dispersity. PIPOx of different M n are used for the synthesis of conjugates with ibuprofen (5 mol %), the nonsteroidal anti-inflammatory drug. The release of ibuprofen at 37 °C and different pH values is monitored using high-performance liquid chromatography, where the rate of drug release increases with increasing pH and lower M n. In vitro cytotoxicity and bioimmunological properties of PIPOx and drug conjugates are studied using 3D reconstructed tissue models of the human epidermis and intestinal epithelium. We demonstrate low cytotoxicity of PIPOx and conjugates with different M n values on both 3D tissue models.