Controlled release using ionotropic polyphosphazene hydrogels

Poly(bis(carboxylatophenoxy)phosphazene) (PCPP) forms hydrogels when treated in aqueous media with salts of divalent cations, such as calcium chloride. This system has potential as a material for the controlled release of drugs. To study the ability of the PCPP hydrogel matrix to release macromolecular substrates, 24-nm fluorescent polystyrene beads or proteins with varying molecular weights were encapsulated in polyphosphazene microspheres. The influence of polyphosphazene concentration and ionic crosslinker content on the outward diffusion of substrates and on microsphere morphology was investigated. In order to create a poly-L-lysine (PLL) outer membrane coating around the PCPP microspheres, the spheres were treated with PLL solution (single coating) or sequentially with PLL and PCPP solutions (double coating). The formation of these membranes (stable poly electrolyte complexes) strongly influences the permeability of the polyphosphazene microspheres and contributes to their stability in physiological saline solution. This enables liquefaction and swelling of the internal core of the microcapsules in saline solution via ion-exchange reactions with monovalent salts and chelating agents. Increasing the PLL molecular weight in the coating process results in a significant enhancement of the substrate release rate. It is possible that the mechanism of this process includes partial coating rupture without loss of bead coherence. The effect of microsphere coating on release profiles can be controlled by varying the molecular weights, the concentration of PLL and reaction times between PCPP microspheres and PLL.