Nucleic acid-based therapies rely on efficient formulations for nucleic acid protection and delivery. As nonviral strategies, polymeric and lipid-based nanoparticles have been introduced; however, biological efficacy and biocompatibility as well as poor storage properties due to colloidal instability and their unavailability as ready-to-use systems are still major issues. Polyethylenimine is the most widely explored and promising candidate for gene delivery. Polyethylenimine-based polyplexes and their combination with liposomes, lipopolyplexes, are efficient for DNA or siRNA delivery in vitro and in vivo. In this study, a highly potent spray-dried nanoparticle-in-microparticle delivery system is presented for the encapsulation of polyethylenimine-based polyplexes and lipopolyplexes into poly(vinyl alcohol) microparticles, without requiring additional stabilizing agents. This easy-to-handle gene delivery device allows prolonged nanoparticle storage and protection at ambient temperature. Biological analyses reveal further advantages regarding profoundly reduced cytotoxicity and enhanced transfection efficacies of polyethylenimine-based nanoparticles from the nanoparticle-in-microparticle delivery system over their freshly prepared counterparts, as determined in various cell lines. Importantly, this nanoparticle-in-microparticle delivery system is demonstrated as ready-to-use dry powder to be an efficient device for the inhalative delivery of polyethylenimine-based lipopolyplexes in vivo, as shown by transgene expression in mice after only one administration.

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We employed indirect rapid prototyping templating to fabricate bioactive and macroporous scaffolds for bone regeneration. This templating technique utilizes lost molds made of polycaprolactone by fused deposition modeling, in which the organic/ inorganic hybrid silica sol was filled and cured. Finally, the molds were dissolved and extracted, and the remaining macroporous hybrid glass constructs were recovered. The hybrid glass scaffolds offered a fully interconnected pore structure with 63-72% porosity measured by N2-pycnometry and Hg-intrusion. In bioactive sol-gel glasses one issue is the insufficient and inhomogeneous incorporation of calcium (II) ions. To address this problem we varied the curing conditions and tested the effect of the organic crosslinker on calcium retention. We strengthened the silica network by covalent crosslinking with trimethylolpropane ethoxylate which was functionalized with 3-(triethoxysilyl)propyl isocyanate. Those scaffolds showed compressive yield strengths of up to 12.7 MPa and compressive moduli between 18 and 288 MPa. Energy dispersive X-ray spectroscopy showed that a crosslinker content of 60% in the hybrids resulted in a homogeneous calcium distribution in the glass, in contrast to 40% where we found a layer of CaCl2 on the scaffold surface. The materials exhibited bioactivity in simulated body fluid which was monitored by scanning electron microscopy and X-ray powder diffraction.