Background: Many different methods have been developed to incorporate hydrophobic
compounds into polymeric micelles, including simple equilibrium (SE) and solvent
casting (SC). Thus far, no studies have compared the SE and SC methods for drug
loading and stability.
Methods: Resveratrol (RES), a model hydrophobic compound, loaded in various Pluronics® (F88, F98, F108,
and F127) is used to determine the differences between SE and SC methods.
Results: Micelles prepared by SE method demonstrated RES loading in proportion to their respective CMC
values with F127 having the lowest CMC and highest loading at Day 14 of 5.39±0.19 mg/mL, followed by
F98 at 3.65±0.13 mg/mL, F108 at 3.29±0.06, and F88 at 2.35±0.05 mg/mL. Initial RES loading in SC method
approaches 10 mg/mL in all the polymers, however, the micelles are unable to retain RES at this concentration
for more than a few hours to a day. At the lower loading of 5 mg/mL a higher stability is seen in the
Pluronic® micelles. In all micelles prepared by SC method, whether high or low loading, over a 14 day period
the RES concentration in the micelles approached the equilibrium RES solubility.
Conclusion: Our results demonstrate that micelles prepared by SC result in meta-stable micelles when the
amount of the compound loaded exceeds the equilibrium loading and the rate at which the compound in the
micelles approaches equilibrium solubility is determined by the hydrophobicity of the compound and the hydrophile-
lipophile balance (HLB) of the polymer.