Supramolecular assemblies of alkane functionalized polyethylene glycol copolymers for drug delivery

Surfactants are commonly used drug carriers, however, there is a lack of understanding regarding the relationship between drug loading, drug release kinetics, and cell internalization with the physicochemical properties of the drug carriers, preventing rational design. The effects of altering hydrophobic and hydrophilic chain lengths on a poly[poly-(oxyethylene)-oxy-5-hydroxyisophthaloyl] (Ppeg) platform for delivering hydrophobic drugs was examined. The synthesized polymers were characterized by nuclear magnetic resonance spectroscopy (NMR), dynamic light scattering (DLS), and zeta potential. The resulting polymer particles were able to form micelles in aqueous solution and encapsulate pyrene, a highly hydrophobic model drug, with a loading capacity up to 8wt%, corresponding to a 50% loading efficiency. The ability to sustain drug release from these micelles over several days was also observed. RAW 264.7 macrophage uptake of the micelles was measured quantitatively and was found to be substantially higher than internalization of the unencapsulated drug. The loading capacity of the drug in the various micelles did not correlate with the internalization of the particles into the cells. Factorial analysis was used to develop predictive equations for drug loading, drug release kinetics, and cell internalization. These models were validated with newly synthesized compounds.