Comparison of PEG chain length and density on amphiphilic macromolecular nanocarriers: Self-assembled and unimolecular micelles

Abstract

Two classes of amphiphilic macromolecules were evaluated for drug delivery applications: those that exist as unimolecular micelles and those that self-assemble in aqueous solution to form micelles. This study compares the poly(ethylene glycol) (PEG) chain length and density that constitute the corona of both classes. In particular, the effect of PEG branching on micellar size, water-solubility, resolubilization rate, drug loading efficiency and drug release rate were analyzed. Pluronic P85 and Cremophor EL, commonly used in pharmaceutical applications, were used as controls. Indomethacin (IMC) was used as the drug for encapsulation, release and resolubilization experiments. Results indicated that smaller micellar sizes, higher water solubilities and faster resolubilization rates were achieved from higher PEG densities compared to linear PEG analog of similar mass. Further, micellar sizes of both higher density PEG and linear PEG macromolecules were constant over a wide temperature range (2–70 °C). In contrast, Cremophor EL formed aggregates at 15 °C and Pluronic P85 underwent a size transition at 45 °C. IMC loading efficiencies for all amphiphilic macromolecules were comparable to controls. However, faster resolubilization and slower drug release were observed for higher density PEG macromolecules compared to linear PEG analogs and controls.