Across the pulmonary epithelial barrier: Integration of physicochemical properties and human cell models to study pulmonary drug formulations.
During the process of inhalable formulation development a deep knowledge of the physicochemical characteristics of the drug and formulation components and the biological properties of the airways is necessary. For example, the solubility and lipophilicity of a drug may affect therapeutic efficacy by changing the residence time of the microparticles at the airway surface. Furthermore, the properties of microparticles, such as shape, size and density, as well as the diseases of the respiratory tract, delivery device and inhalation manoeuvre will have an impact on where these microparticles are deposited. The airway epithelium is involved in the pathogenesis and treatment of respiratory diseases. Epithelial cells are directly exposed to the environment and respond to xenobiotics. In some cases, they are the site of action for drug molecules or the drug molecules might need to be transported across the epithelium to arrive at the site of action. The drug particles deposited on the respiratory epithelia have to interact with the mucus lining, dissolve and get transported through this layer. Despite advances in in vitro testing of respiratory epithelial permeability, there is little known about how and where drugs are absorbed at a cellular level and how long they reside in the lung. Therefore, pulmonary permeability assessment of drugs may provide insights that will allow formulations to be developed with optimised therapeutic outcomes. This review focuses on the integration of these physicochemical characteristics with the biological factors to provide a better understanding of the fate of microparticles after deposition on the epithelial cells.
Respiratory Technology, Woolcock Institute of Medical Research, NSW 2006, Australia; Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2006, Australia. Electronic address: mhag6035@uni.sydney.edu.au.
Mehra
M
Haghi
Respiratory Technology, Woolcock Institute of Medical Research, NSW 2006, Australia; Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2006, Australia.
Hui Xin
HX
Ong
Respiratory Technology, Woolcock Institute of Medical Research, NSW 2006, Australia; Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2006, Australia.
Daniela
D
Traini
Respiratory Technology, Woolcock Institute of Medical Research, NSW 2006, Australia; Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2006, Australia.
Paul
P
Young
D065567:Absorption, Physiological; D001692:Biological Transport; D002460:Cell Line; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D015195:Drug Design; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D010599:Pharmacokinetics; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism; D013499:Surface Properties
D004364:Pharmaceutical Preparations
Absorption; Cell culture; Deposition; Epithelia; Pulmonary delivery; Transport