Sustained release of therapeutic proteins from multilayers adsorbed on the sidewalls of porous membranes

Abstract

Controlled drug release system employing degradable thin films has recently received much attention owing to many potential applications in biomedical approaches. The layer-by-layer assembly is one of powerful tools to realize such controlled release system because of the ability to easily incorporate biomaterials such as DNA, proteins, and peptides within the film in mild aqueous conditions and those multilayered films undergo gradual disassembly under physiological conditions. However, it has been regarded as a challenging task to prevent the initial burst release of active agents as the multilayer films are immediately degraded from the early stage. In the present study, in order to prevent such an initial fast release, we have employed cylindrical porous structures since the effective diffusion coefficient of a solute within pores is known to be lower than the value in the bulk state, resulting from hydrodynamic and entropic restriction on the solutes due to the presence of pore walls. By varying the pore size of porous membranes, we could modulate the release kinetics of a model protein incorporated within multilayered films, allowing the release of proteins in a more sustained manner when compare with the release from a flat substrate without any additional controlled parameters.