Insights into Morphological Transition of Pluronic P123 Micelles as a Function of Gallate

Pluronics have emerged as a potential agent for solubilizing a variety of lipophilic bioactive molecules, but how these solubilizates affect the morphology of Pluronic micelles still remains poorly understood. In this work, the morphological transition of Pluronic P123 micelles induced by three gallate homologs with different alkyl chain length, namely methyl gallate (MG), propyl gallate (PG) and octyl gallate (OG) has been comprehensively investigated by combination of dynamic light scattering (DLS), cryogenic transmission electron microscopy (Cryo-TEM), 1H NMR and atom-scale molecular dynamic simulations. It is found that addition of the three gallate significantly increases the micellar sizes and polydispersities. Cryo-TEM measurements reveal that spherical P123 micelles form micellar clusters in the presence of PG and short rod micelles with OG, while MG do not change the micellar morphology. Qualitative interactions between various gallate and P123 micelle are determined by NMR experiments. It is demonstrated that the different locations of various gallate in the micelles are governed by the balance of hydrophobic interaction and hydrogen bonding, which consequently leads to the varying micellar morphologies. The experimental results are further confirmed by dynamic molecular stimulation. We also show that the intensity of Pluronic-gallate interaction increases with the hydrophobicity of the gallate, indicating that hydrophobic interaction is more important on the morphological transition. Finally, the mechanism of morphological transition induced by various gallate are discussed and proposed, where the nature of formation of micellar cluster induced by PG is particularly emphasized.