Synthesis Of Polyelectrolyte Capsules

Polyelectrolyte capsules are fabricated by layer-by-layer adsorption (LbL). This technique is based on the consecutive assembly of oppositely charged synthetic polymer layers around a preformed charged spherical core. At the end of the LbL adsorption process, the cores can be successfully removed to obtain hollow and stable capsules whose inner cavity and polymer wall can be loaded and functionalized, respectively, with a variety of substances such as molecular dyes, drugs, nanoparticles and bimolecular, which retain their distinctive properties after the embedding procedure (fig 1). The resulting hollow capsules usually have a wall thickness of between a few tens and several hundreds of nanometers and a diameter ranging from tens of nanometers to several micrometers depending, on the size of the original core.

Fig. 1. Schematic of polyelectrolyte capsule fabrication by layer-by-layer (LbL) assembly. (i) Initial electrostatic adsorption of a negatively charged polymer onto a positively charged template core. (ii) Second adsorption of positively charged polymer onto the now negatively charged template. (iii) Multilayer growth via alternating adsorption of oppositely charged polymers. (iv) Removal of the template by dissolution to obtain a capsule with an empty cavity. Capsules are not drawn to scale.

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Self-assembly of the subsequent layers is governed by the strong electrostatic interactions that occur between the oppositely charged layers in solution, resulting in overcharging of films after deposition of each layer. Based on this phenomenon, the fabrication of multilayered polymer capsules is a highly versatile procedure, since it depends on the capability of a charged molecule to be consecutively adsorbed onto the top of an oppositely charged surface/layer. Thus, the two fundamental components for capsule fabrication are the core templates and the polyelectrolyte pairs (fig 1).

An ideal template has to be stable under the LbL process, soluble in mild conditions, and completely removable from the inside of the capsules, without affecting the morphology and stability of the multilayer assembled on top of it. In recent years, numerous materials have been employed as sacrificial templates, such as (i) polystyrene latex, (ii) melamine formaldehyde, (iii) SiO₂, (iv) carbonate particles (MnCO₃, CaCO₃, CdCO₃), and (v) biological cells. Such materials can be dissolved by solvents like (i) tetrahydrofuran (THF), (ii) hydrochloric acid (HCl), (iii) hydrogen fluoride (HF), (iv) ethylene diamine tetraacetic acid (EDTA), and (v) saline solution (e.g. sodium hypochlorite solution), respectively. However, advantages and disadvantages are observed in each of the dissolution procedures and great efforts are currently being focused on the development of new cores that could merge all the above requirements within a unique material.

The capsule wall composition also plays a crucial role for the fabrication of functional capsules, as their permeability/porosity strongly depends on the chemical structure and the molecular weight of the employed polyelectrolyte pairs. The majority of polyelectrolyte capsules described in the literature are composed of pairs of synthetic anionic poly (sodium) styrene sulfonate and cationic poly(allylamine) hydrochloride. Although these multilayers are known to have numerous advantages, for therapeutical purposes there is a special interest in using more biocompatible materials, which are potentially biodegradable under physiological conditions. Enzymatically degradable multilayer capsules have already been described. Another strategy utilizes proteins as layer forming materials. Thanks to their amphoteric properties, their charge can be tuned by varying the pH value below or above their isoelectric point to obtain polycation or polyanion layers.

The mechanical/elastic properties of polyelectrolyte capsules are influenced by several parameters, such as the chemical nature of the polymers used (which can cause weak or strong intermolecular interactions within the multilayer) and the molecular composition of the inner part of the capsules. In particular, atomic force spectroscopy studies have shown that capsules with elasticity ranging within 0.05–10 GPa can be obtained depending on the composition, treatment, and filling of the capsule.

Several methods, such as electrophoretic mobility and light scattering measurements are typically used to follow the layer growth of polyelectrolytes onto the spherical templates, while for their structural characterization, both electron and atomic force microscopy are commonly employed.

Finally, confocal laser scanning microscopy analysis is widely used for real-time observation of core dissolution in vitro to characterize the permeability properties of these capsules, their cellular uptake, and the subsequent intracellular release of the encapsulated materials.