Immunological and toxicological implications of short-term studies in animals of pharmaceutical aerosol delivery to the lungs: Relevance to humans

Abstract

The effects of xenobiotics on the lungs have been studied for many years. In the past 50 years, delivery of drugs to the lungs has been adopted to achieve local effects, specifically for the treatment of asthma. Recently, due to the proximity of the circulating blood supply and to their large surface area, the lungs have been proposed as the port of entry for drugs to obtain systemic effects, particularly for macromolecular compounds of biological origin. Numerous studies regarding drug formulation, delivery systems, and related pharmacokinetics have been reported; however, the concurrent effects of pulmonary delivery of drugs on the physiology of the lung has not been evaluated early in the development process. The prospect of using the lungs for the delivery of biological molecules such as proteins, peptides, and nucleic acids raises the question of the local toxicity of these compounds. Therefore, criteria must be established to study the initial impact of pulmonary drug delivery on the physiology of the lungs. This relates particularly to subtle local and systemic implications of those effects on the transport phenomena that may be contrasted with conventional toxicity studies focused on gross effects