Sonication parameters for the preparation of biodegradable nanocapsules of controlled size by the double emulsion method

The main goal of the present work was to study the influence of the sonication process on the characteristics of poly(lactide-co-glycolide) nanocapsules prepared by the water-in-oil-inwater solvent evaporation method. The duration and intensity of sonication were investigated with respect to their ability to modify the size and distribution of the nanocapsule population. It has been demonstrated that the duration of the second mixing step (leading to the w/o/w emulsion) is of greater influence than that of the first step (water-in-oil emulsion) on the final mean particle size. A three-dimensional response surface was drawn up to show that when the second emulsification time increased, the mean size decreased until reaching a plateau. A threshold in sonication intensity also exists, allowing optimization of both parameters and the formation of nanocapsules of controlled size with a rather narrow distribution. The use of a vortex mixer instead of a sonicator during the first mixing step led to nanocapsules with a similar response surface, supporting the idea that the second step is the decisive one. Finally, nanocapsules loaded with methylene blue, a hydrophilic model compound with a positive charge, were characterized and the encapsulation efficiency calculated. Their size and distribution were similar to that of the blank nanocapsules. Entrapment efficiency was independent of duration, intensity, and type of mixing. From these results, it was concluded that nanocapsules of controlled size could be obtained upon optimizing certain process parameters.