Bulking up: the impact of polymer sterics on emulsion stability

Encapsulation of hydrophobic active ingredients is critical for targeted drug delivery as water-insoluble drugs dominate the pharmaceutical marketplace. We previously demonstrated hexadecane-in-water emulsions stabilized with a pH-tunable polymer, poly(acrylic acid) (PAA), via a steric layer preventing particle aggregation. Using vibrational sum frequency scattering spectroscopy (VSFSS), here we probe the influence of steric hindrance on emulsion colloidal stability by tailoring the molecular weight of PAA and by adding an additional methyl group to the polymer backbone via poly(methacrylic acid) (PMAA) at pH 2, 4, and 6. At low polymer molecular weight (2 and 10 kDa), PAA adsorption is entropy driven and akin to surfactant-mediated stabilization. With 450 kDa PAA, the longer polymer chain emphasizes enthalpically favored polymer-oil interactions to initially coat the surface, and forms layers at increasing molecular weight (1000 and 4000 kDa). PMAA exhibits better oil-solubility than PAA at low concentrations but cannot accommodate the steric hindrance at higher concentrations leading to disorder. Finally, we connect our molecular-level understanding of PAA ordering with temperature-dependent dynamic light scattering experiments and observe that emulsions coated with PAA at pH 2 and 4 maintain colloidal stability from 0-90 °C, making PAA a promising polymer for hydrophobic drug delivery.