Polymeric nanocontainers with high loading capacity of hydrophobic drugs

Water soluble 4- and 6-arm star-shaped polymers with (bio) degradable hydrophobic cores and dense hydrophilic coronas were synthesized by a combination of ring opening polymerization (ROP) and atom transfer radical polymerization (ATRP). Their carrier abilities of different model compounds as well as active pharmaceutically ingredients in aqueous solutions were evaluated by UV/Vis and H-1 NMR spectroscopy studies. The highest loading capacities (up to 36 guest molecules per molecule of polymer) were, as expected, found for the 6-arm star-shaped polymers. The densely grafted poly[poly(ethylene glycol) methyl ether methacrylate] [p(mPEGMA)] shell stabilizes the host-guest complexes preventing undesired multimolecular aggregation. Dynamic light scattering (DLS) measurements evidenced the unimolecular character of all 4- and 6-arm polymers before and after loading with guest molecules. The (bio) degradability of the core was demonstrated under acidic conditions and in vitro using a lipase from Rhizopus Arrhizus. The dual-stimuli responsiveness of the hydrophobic core to enzymes and pH may facilitate increased control over in vivo drug release.