Controlling the internal morphology of aqueous core-PLGA shell microcapsules: promoting the internal phase separation via alcohol addition.

The ability to control the internal core architecture of polymeric microcapsules has a direct impact on their applications. However, this task, especially to produce microcapsules with a high percentage of mononuclear aqueous cores, proved to be challenging. In this work, and in continuation to our previous studies, we report a facile protocol to prepare poly(D,L-lactide-co-glycolide) (PLGA) microcapsules with unprecedented percentage (almost 100%) of mononuclear aqueous cores by the internal phase separation method via adding alcohols. Different types of alcohols (methanol, ethanol, propanol, isopropanol, butanol, and octanol) were incorporated into the internal phase solution and then emulsified into mineral oil. In situ monitoring of emulsion droplets was performed by phase contrast microscopy at different time points and the percentage of mononuclear droplets was measured. While alcohol-free formulation ended up with only around 51% of mononuclear microcapsules, incorporating alcohols resulted in the formation of more than 90% of mononuclear microcapsules. Octanol, in particular, exhibited an outstanding performance as its incorporation led to an immediate (at 0 h) formation of almost entirely mononuclear microcapsules. Final microcapsules exhibited spherical shape with mean particle size in the range of 1-2 µm as depicted by scanning electron microscopy and dynamic light scattering analysis.