August 21, 2006
Nanoparticle Design Influences Inflammatory Potential in Lung
Drug developers consider the lungs to be an excellent route through which to administer drugs. Many studies have shown that inhaled nanoparticles, including those from natural sources, can trigger inflammation in the lungs, raising concerns that have slowed efforts to develop inhalable nanoparticle drug delivery systems for anticancer agents. Those concerns may be alleviated thanks to new findings that nanoparticles made of biodegradable materials do not trigger inflammation.
Werner Seeger, Ph.D., of the University of Giessen, in Germany, led a team of investigators who compared the inflammatory effects of biodegradable and non-biodegradable nanoparticles delivered into the lungs. The researchers tested nanoparticles made of biostable polystyrene, biodegradable poly(lactic-co-glycolic acid) (PLGA), and a novel biodegradable polymer made of PLGA linked to a second polymer known as poly(vinyl alcohol) (PVA). This latter polymer is considered a strong candidate for pulmonary delivery of pharmaceuticals.
Using both cultured lung cells and mice, the investigators found that polystyrene triggers a substantial inflammatory reaction. In comparison, PLGA nanoparticles of the same size produced no more of an inflammatory response than did a dilute salt solution. PLGA-PVA nanoparticles did not trigger any signs of inflammation, either. The researchers noted, however, that the larger PLGA-PVA nanoparticles were cleared more rapidly from the lungs by macrophages, which would not be desirable for a drug delivery vehicle.
This work is detailed in a paper titled, “Investigation of the proinflammatory potential of biodegradable nanoparticle drug delivery systems in the lung.” An investigator from King’s College of London also participated in this study. An abstract of this paper is available through PubMed.