Monday, 05 November 2012 21:01

Saarbrücken: Nano-drug ferry to trick biological barrier Featured

Scientists from the Department of Pharmacy at the Saarland University and the Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS) have developed a drug-delivery system that looks like a corn cob.

Biological barriers such as the mucous membranes of the lungs often make it difficult for drugs to reach their target sites. Scientists from the Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS) at Saarland University led by Prof. Claus-Michael Lehr and Junior Professor Dr. Marc Schneider, Department of Pharmaceutical Nanotechnology, have recently discovered that in lung mucus a stiff gel scaffold separates large fluid-filled pores from each other and prevents the movement of nanoparticles via pore boundaries similar to the bars of a cage. The researchers are looking into the development of drug delivery systems and have developed a drug ferry able to outsmart this biological barrier.

The ferry consists of cylindrical or tubular nano-rods. The tube is 10 micrometres long and the diameter of the beads is 800 micrometres. The particles look like corn on a cob. The intention is to later be able to apply drugs to this array.




Photo: Marc Schneider / Saarland University


At present, the ferry is made of silica particles; however, this material will be replaced by biodegradable material in a following step. After inhalation, the rods reach the respiratory epithelium, but cannot easily pass it. Here is where most of the lung’s alveolar macrophages are located. Alveolar macrophages are the immune system’s scavenger cells and fulfil many functions in the air sacs (alveoli), such as lung cleaning by ingesting foreign particles such as dust or pathogens. They are also involved in inflammation processes and hypersensitivity reactions. The example of asbestos demonstrates this: Since asbestos is not a pathogen and cannot be eliminated by an immune response, it can lead to a permanent state of inflammation. Continuous deposits of the material in the macrophages can lead to the formation of granulomas, which can then result in pulmonary fibrosis or lung cancer.

The alveolar macrophages phagocytise (ingest) the rod-like ferries deposited on the lung epithelium, but cannot digest the inorganic silica compound, otherwise can transport the ferries to other regions of the lung. The ingestion process itself is slow and takes up to three hours. However, the plan is that in the meantime the ferry should have released the drug, which then makes its own way through the labyrinth of mucus and gel rods until it arrives at the target site. The nano-ferry is no longer needed and can be dissolved by the macrophages. To achieve this, it is planned to produce a new type of ferry consisting of sugars or alginates.

“With rod shape, we want to achieve two goals”, says Professor Marc Schneider. “On the one hand, the large rod shape can penetrate into the deeper lung layers; on the other hand the arrangement of the pellets increases the surface area, allowing more of the active agent to be transported.” For their studies the researchers use cell culture models with human lung cell types which can mimic the human lung barrier.

Recently they received the second prize in the German nationwide photo contest “Nano-Momente 2012” for a scanning electron microscopic photo (see above).

For more information (in German): http://www.uni-saarland.de/nc/aktuelles/artikel/nr/6827.html