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The transport of macromolecular drugs such as oligonucleotides into the lungs has become increasingly relevant in recent years due to their high potency. However, the chemical structure of this group of drugs poses a hurdle to their delivery, caused by the negative charge, membrane impermeability and instability. For example, siRNA to reduce tumour necrosis factor alpha (TNF-α) secretion to reduce inflammatory signals has been successfully delivered by inhalation. In order to increase the effect of the treatment, a co-transport of another anti-inflammatory ingredient was applied. Combining curcumin-loaded mesoporous silica nanoparticles in nanostructured cylindrical microparticles stabilized by the layer-by-layer technique using polyanionic siRNA against TNF-α was used for demonstration. This system showed aerodynamic properties suited for lung deposition (mass median aerodynamic diameter of 2.85 ± 0.44 µm). Furthermore, these inhalable carriers showed no acute in vitro toxicity tested in both alveolar epithelial cells and macrophages up to 48 h incubation. Ultimately, TNF-α release was significantly reduced by the particles, showing an improved activity co-delivering both drugs using such a drug-delivery system for specific inhibition of TNF-α in the lungs.

A novel type of microparticle has recently been engineered. It consists of amorphous silica nanoparticles and has a corncob-like shape. It has already been demonstrated in vivo that alveolar macrophages in the lung are able to engulf this particulate carrier and that it also functions successfully as a gene delivery system. This subsequently raises the question as to whether epithelial cells may also be possible targets for these microrods. For this purpose, the alveolar epithelial cell line A549 was used presently. The epithelial character of these confluent cells was documented by the presence of tight junctions using a freeze-fracture technique and transmission electron microscopy. A toxic effect of the particles incubated with these cells was largely excluded. The interaction of the microparticles with the epithelial cells was observed using confocal microscopy and live cell imaging. Interestingly, the particles entered the epithelial cells within hours. After 1 day, the intracellular particles began to disaggregate and release the silica nanoparticles. Thus, even epithelial cells may serve as targets for this novel carrier and gene delivery system. This is particularly important since safe and effective gene delivery remains an unsolved problem. In addition, delivery of anti-cancer and anti-infective drugs may be an application of this novel particulate carrier.

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