Novel approaches to enhance pulmonary delivery of proteins and peptides

Abstract

In the last two decades, large efforts have been made to develop safe methods for the delivery of proteins and peptides via the lungs into blood circulation for treatment of systemic diseases. For this purpose, a number of biophysical and physiological parameters have to be considered, such as particle diameter, particle density, hygroscopicity, electrical charge, chemical properties of the substance and age, pulmonary diseases, breathing pattern, all of which affect the mechanisms of pulmonary drug deposition. Variations in these parameters result in a substantial change of particle deposition in the lung. For example, large particles (>10 microm) are not able to penetrate into the lung, because they are deposited by impaction in the upper respiratory tract. On the other hand, small particles (0.1-1.0 microm) are inspired into the alveoli but also expired without being deposited significantly. Particles of diameters 2-4 microm show the ideal pulmonary deposition behavior and are able to transport a substantial mass of pharmaceuticals into the lung. Modifications of breathing pattern allow an optimal particle deposition in the bronchial or the alveolar region. In addition, particle deposition in the alveolar region is the basis for treatment of systemic diseases by inhalant administration of drugs (e.g., insulin). This paper deals with the physical and physiological basics for inhalation therapy and demonstrates novel systems which were designed to optimize drug delivery into the lung periphery. The AKITA inhalation system is an example for a system that guides the patient through the inhalation maneuver and ensures an optimized particle deposition and a minimized intersubject variability.