**3.3 Layer-by-layer method (LBL)**

The layer-by-layer method has a great potential to develop multi-compartmental delivery devices since nanocapsules with multiple polymeric layers around the core are obtained. This method requires a colloidal core, which can be the solid form of the active substance, inorganic particles, biological cells, or an oil-in-water nanoemulsion prepared using any of the methods described in Section 3.2. The mechanism of this nanocapsules formation is the irreversible electrostatic attraction—a sequential adsorption of oppositely charged polyelectrolytes is achieved [5, 37]. The sequential deposition of polycations and polyanions on the inorganic core can be followed by the sacrifice of the template core, resulting in a hollow nanocapsule where the payload can be trapped [6, 38, 39]. The main advantages of the LBL technique are the possibility to simultaneously encapsulate different drugs at different positions, and the possibility to control release properties by modulating the composition and the thickness or number of layers of the polymeric shell [24, 40, 41]. On the other hand, this method bears some difficulties, such as the separation of the polyelectrolyte and the remaining counterions in each deposition cycle. Otherwise, aggregates of these may form. This high number of assembly steps is quite complex and time-consuming. In addition, larger nanocapsules are obtained compared to other methods, due to the number of polymeric layers deposited [21].
