Search Results (2)

Addressing the challenge of efficient drug delivery to the lungs, a nano-structured, microparticulate carrier system with defined and customizable dimensions has been developed. Utilizing a template-assisted approach and capillary forces, particles were rapidly loaded and stabilized. The system employs a biocompatible alginate gel as a stabilizing matrix, facilitating the breakdown of the carrier in body fluids with the subsequent release of its nano-load, while also mitigating long-term accumulation in the lung. Different gel strengths and stabilizing steps were applied, allowing us to tune the release kinetics, as evaluated by a quantitative method based on a flow-imaging system. The micro-cylinders demonstrated superior aerodynamic properties in Next Generation Impactor (NGI) experiments, such as a smaller median aerodynamic diameter (MMAD), while yielding a higher fine particle fraction (FPF) than spherical particles similar in critical dimensions. They exhibited negligible toxicity to a differentiated macrophage cell line (dTHP-1) for up to 24 h of incubation. The kinetics of the cellular uptake by dTHP-1 cells was assessed via fluorescence microscopy, revealing an uptake-rate dependence on the aspect ratio (AR = l/d); cylinders with high AR were phagocytosed more slowly than shorter rods and comparable spherical particles. This indicates that this novel drug delivery system can modulate macrophage uptake and clearance by adjusting its geometric parameters while maintaining optimal aerodynamic properties and featuring a biodegradable stabilizing matrix. Full article

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. Full article