Formulation and Evaluation of Protein Based Nano Particulate System For Treatment of Pulmonary Infections

In addition to the so-called small molecule drugs, proteins and peptides are of increasing interest for pharmacotherapy, due to several advantageous properties. In general, those compounds are administered parenterally. However, non-invasive routes of administration represent a great part of research. Amongst others is the pulmonary application of proteins and peptides for local delivery in the case of pulmonary diseases, such as idiopathic pulmonary fibrosis, where the alveolar epithelium is affected. To ensure an intracellular delivery, nanoparticles in a size range of 150 nm were prepared via charge-mediated coacervation, characterized for their physicochemical properties and loaded with several model-proteins and -peptides. The material used for nanoparticle preparation was chosen to be positively and negatively charged starch derivatives, which were synthesized from potato starch. Although nanoparticles in that size range are known to show an increased cell uptake, they do not show a high deposition in the deep lung. Thus, an advanced carrier system consisting of a fast dissolving microparticle matrix with embedded starch nanoparticles was developed and characterized. Due to its aerodynamic properties, that carrier system was able to deposit a high fraction of the applied dose in the deep lung (~50%), while at the same time demonstrating (in in vitro models) the ability to facilitate uptake of starch nanoparticles into cells of the alveolar epithelium after fast dissolution of the microparticle matrix.