Maintaining Small Molecule Supersaturation in a Diblock Micelle Corona Reservoir

In this study, poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (PND) statistical copolymers and a series of poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)-b-polystyrene (PND-b-PS) diblock polymers were synthesized, in which the molecular weight of the PND corona block was kept constant while the polystyrene core block length was varied. Corona region of the micelle, rather than the core, was utilized as a reservoir to store hydrophobic small molecules. Small molecule crystallization was inhibited by partitioning to micelle corona, resulting in enhanced small molecule supersaturation. Solution-state properties of the polymers were quantified by dynamic light scattering, small angle x-ray scattering and cryogenic transmission electron microscopy. Diffusion coefficients of two hydrophobic model drug molecules were measured in presence of the polymers by pulsed field gradient NMR spectroscopy, from which the drug-polymer “binding” constants were quantified. The in vitro dissolution of both drug molecules was systematically investigated as a function of composition and solution-state assembly of the polymers. The corona loading strategy demonstrated in this study can be potentially applied to store any hydrophobic small molecules with proper design of the polymer micelle.