Aspherical, nanostructured microparticles for targeted gene delivery to alveolar macrophages : [Asphärische, nanostrukturierte Mikropartikel zur gezielten Transfektion alveolarer Makrophagen]

Abstract

Cylindrical and nanostructured microparticles were prepared by a template-assisted engineering technique. The particles were stabilized and loaded by a functional layer-by-layer (LbL) coating with plasmid-DNA (pCMV-luciferase) and branched polyethylenimine. Due to their size and shape, particles are especially qualified for pulmonary delivery. In addition, the particles are exclusively taken up by phagocytes adding specific targeting to the system. The luciferase expression is demonstrated in macrophages showing increasing levels over a time period of at least 7 days. Furthermore, it is for the first time shown that the expression is depending on the LbL design. In in vivo experiments luciferase expression is only observed in mice alveolar macrophages. Combining site specific transport with the possibility of genetically engineering immunocompetent phagocytes, the presented system offers promising potential to improve applications for cell-based immunotherapies.