Designing LbL Capsules for Drug Loading and Release

Layer-by-layer (LbL) [1] assembly is a powerful tool for engineering microparticulate structures. On the one hand it allows one to tailor the surface chemistry of microparticles, rendering them responsive to physicochemical stimuli such as pH, ionic strength, light, and so on, to allow bio-specific recognition or just to prevent adsorption of unwanted species [2]. On the other hand, using microparticles as sacrificial templates, one can fabricate spherically-shaped free-standing polymeric multilayer films, forming hollow capsules [3–5]. These capsules are formed in multiple steps. First, alternating polymeric layers are deposited onto core microparticles. Typically electrostatics or H-bonding [6–8] between the successive layers is used as the driving force for this multilayer build-up. Secondly, the core microparticles are decomposed into lowmolecular weight degradation products which can freely diffuse through the LbL membrane. The resulting hollow capsules have walls with a thickness of typically a few tens of nanometers and surround an aqueous void. From this conceptual point of view, LbL capsules form a binary system in which both the LbL membrane and the hollow void can be exploited to perform a specific function. As the primary focus of our research laboratories lies in the field of drug delivery, we will present in this chapter several approaches that we have developed in applying LbL technology to the design of drug delivery systems. For drug delivery purposes, two aspects are crucial: (i) something should be encapsulated inside the capsules and (ii) the encapsulated content should be released. Themost evident route for encapsulation is without doubt the incorporation of drug molecules within the hollow void of LbL capsules, while engineering the LbLmembrane to be responsive to specific physicochemical stimuli looks a straightforward way to release encapsulated material. In collaborationwith the Sukhorukov groupwe developed several strategies that allowed encapsulation of macromolecular drugs into capsules using pre-loaded microparticulate templates. Furthermore, we explored several possibilities to design LbL capsules that could release their payload in a controlled fashion, not only by engineering the LbL membrane, but also by engineering the core templates.