Increasing drug or nutrient loading in nanocarriers is of interest to developing new drug or nutrient delivery technologies. It is of interest to develop approaches that can maximize the loading capacity of block copolymer micelles, which are important nanocarrier systems.  Experiments show that when the hydrocarbon molecule is a good solvent for the hydrophobic block of the copolymer, one can achieve high equilibrium solubilization capacities of the order of 1 to 3 g of the hydrophobic molecule per g of the hydrophobic block of the copolymer.  However, despite their hydrophobicity, rarely drug molecules constitute good solvents for the polymer blocks.  Therefore, a generic method that could maximize the micelle loading is desirable, independent of the specificity of the drug or nutrient molecule.  We explore through thermodynamic modeling whether the loading capacity of micelles can be increased by manipulating how micelles containing solubilizate are prepared. It is widely recognized that a vast number of micelles generated in water from amphiphilic block copolymers are non-equilibrium structures because of the strong hydrophobicity of the hydrophobic block of the copolymer. Typically, the micelles are prepared by a kinetic process, first allowing molecular scale dissolution of the block copolymer in a common solvent that likes both the blocks and then gradually replacing the common solvent by water to promote the hydrophobic blocks to aggregate and create the micelles. By incorporating the solubilizate during the micelle preparation process we may be able to “freeze” the micelles at conditions where the solubilizate loading is high. The properties of the solubilizate, the choice of the common solvent and their interactions with the hydrophobic block of the copolymer all control the eventual micelle size and loading capacity.  The theoretical model predicts this micelle loading capacity as a function of the molecular parameters that control the formation of solubilizate carrying frozen micelles.

How to increase micelle loading by manipulating the preparation approach for frozen block copolymer micelles? A theoretical view

256th National Meeting (2018)

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