FOR 627:  Polymeric Nano-carriers for Pulmonary Drug Delivery

• Subject Area: Medicine ; Chemistry
• Term: from 2006 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 13983386

Nanoscale objects have stimulated the expectation that new material properties can be attained. These advances have been summarised under the term "Nanotechnology". More recently "Nanomedicine" emerged as a research area, embracing nano- and biomedical sciences. Information on biological properties of nano-objects and their therapeutic application is still scarce. In this Research Unit the performance of different nano-carriers from synthetic polymers will be evaluated in the context of pulmonary delivery. The carriers comprise nanoparticles, polyelectrolyte complexes and nanofibres and nanorods. Size, surface charges and surface properties can be engineered using new biomaterials and new manufacturing techniques. Delivery of conventional drugs, siRNA and DNA will be studied in the context of local pulmonary drug delivery in different disease models. An interdisciplinary Research Unit was formed and entitled "NANOHALE", including scientists from polymer chemistry, polymer physics, pharmaceutics, toxicology, pharmacology and pneumology. The basic concept of NANOHALE consists in the idea that inhaled nano-carriers could allow both a control of spatial and kinetic presentation of drugs to lung tissue, allowing targeting of drugs to diseased tissues. Due to their size (< 250 nm) also cellular uptake and intra-cellular distribution can be manipulated. Coupling of ligands to nanoobjects (folate, antibodies) could allow selective uptake into cells by active targeting. The impact of material properties on cell targeting and distribution will be studied in detail to allow new therapeutic approaches to the local treatment of lung diseases. The tool box of nanoobjects contains nanofibres and nanorods (Greiner/Wendorff), nanoparticles and nanocomplexes (Kissel), and lipid-modified nanoparticles (Bakowsky) produced from biodegradable materials. These nanoobjects will be evaluated in regard to their toxicological properties both on an intro level and in animal inhalation studies (Schulz/Kreyling). The therapeutic application will be evaluated in three model projects addressing the inhalation treatment of micro-metastases in the lung using siRNA (Aigner/Czubayko), pulmonary-selective gene transfer using non-viral vectors for treatment of pulmonary hypertension (Fink/Grimminger), and controlled release properties of nanoobjects for treatment of lung diseases (Gessler/Seeger).

• DFG Programme: Research Units

Projects

• Controlled Release von Wirkstoffen aus nanostrukturierten Carriersystemen in der Lunge (Applicant Gessler, Tobias )
• Dosimetrie und Toxikologie von Nanocarriern für die Therapie von Erkrankungen der Atemwege und des pulmonalen Gefäßbettes (Applicant Kreyling, Ph.D., Wolfgang G. )
• Entwicklung von polymeren nanostrukturierten Carriersystemen für lokoregionale Wirkstoffapplikationen in der Lunge (Applicants Greiner, Andreas ;  Wendorff, Joachim H. )
• Lipidierte nanoskalige Wirkstoffträger für ein selektives Targeting zu entzündeten Bereichen der Lunge, deren Herstellung und physikalisch-chemische Charakterisierung (Applicant Bakowsky, Udo )
• Polyethylenimin-Nanopartikel als inhalativ applizierbare nicht-virale Vektoren zum pulmonalselektiven somatischen Gentransfer (Applicant Fink, Ludger )
• Supramolekulare Nanocarrier zur pulmonalen Verabreichung von Wirkstoffen (Applicant Kissel, Thomas )
• Therapie pulmonaler Metastasen durch die Freisetzung von therapeutischen RNA-Molekülen aus polymeren Nanopartikeln (Applicant Aigner, Achim )

• Spokesperson: Professor Dr. Thomas Kissel