Aerosol Drug Delivery Optimization by Computational Methods for the Characterization of Total and Regional Deposition of Therapeutic Aerosols in the Respiratory System

The intake of medicines in form of aerosols is becoming increasingly popular, especially in the treatment of different lung diseases and allergies. In addition, there is a great interest to utilize the inhalation pathway for systemic therapy. Hence, determination of the required local distribution of inhaled therapeutic aerosols within the respiratory system is a key issue of modern aerosol drug design. In general, deposition characteristics of inhaled particles depend on the properties of the aerosols, the breathing mode and the geometry of the airways. All three parameters must be analyzed for the optimal design of therapeutic aerosols. A recommended way of drug inhalation may differ for various illnesses and patients. There are two different modeling directions for the description of deposition characteristics of inhaled drugs in the respiratory system. One way is the application of lung deposition models for the determination of total, regional and airway generation-specific deposition, and the other way is the usage of computational fluid dynamics techniques for the characterization of local deposition patterns, which, at present, cannot be applied to the whole respiratory system. This computational fluid dynamics approaches will be analyzed in another study. This work describes the general background of aerosol drug delivery optimization, summarizes previous important studies in the field, and provides a comprehensive discussion about numerical lung modeling and the salient features of the newest models and techniques. In the last part, the stochastic lung deposition model is applied to determine the optimal particle size and breathing technique for bronchial and pulmonary drug delivery.