Poly(2-oxazoline) Homopolymers and Diblock Copolymers Containing Retinoate ω-End Groups

Hepatic stellate cells are the vitamin A storing cells of the liver and play a pivotal role in the progression of fibrotic liver diseases through the deposition of the extracellular matrix. To target therapeutically hepatic stellate cells, vitamin A was used in amphiphilic poly(2-oxazoline) (POx) block copolymers with terminal retinoate moieties. Several POx with varying fractions of the hydrophilic block were synthesized by sequential cationic ring-opening polymerization of 2-n-nonyl-2-oxazoline and 2-ethyl-2-oxazoline, followed by termination with in situ deprotonated all-trans-retinoic acid. Characterization utilizing size exclusion chromatography, 1H nuclear magnetic resonance (NMR) spectroscopy, and matrix-assisted laser desorption/ionization time of flight mass spectrometry verified the successful functionalization. Nanoparticle and micelle pairs of similar composition with and without the retinoate moieties were prepared by nanoprecipitation and emulsion techniques. Cellular uptake studies in mouse embryonic fibroblasts expressing a STRA6-like receptor revealed increased uptake of the vitamin A-modified carrier when the hydrophilic POx segments were long enough to prevent the interaction of the hydrophobic retinoate moiety with the hydrophobic carrier core.