Advancements in Protein based Nano Particulate system for treatment of Pulmonary Infections- A Review

Abstract

In addition to the so-called small molecule drugs, proteins and peptides are of increasing interest forpharmacotherapy, 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, nano particles in a size range of 150 nm will be prepared via charge-mediated coacervation, characterized for their physicochemical properties and loaded with several model-proteins. The material used for nano particle preparation was chosen to be positively and negatively charged starch derivatives, which were synthesized from potato starch. Although nano particles 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 micro particle matrix with embedded starch nano particles will be developed and characterized. Due to its aerodynamic properties, that carrier system must be 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 nano particles into cells of the alveolar epithelium after fast dissolution of the micro particle matrix.