Transport mechanisms at the pulmonary mucosa: implications for drug delivery

ABSTRACT

Introduction: Over the past years, a significant number of papers have substantiated earlier findings proposing a role for drug transporter proteins in pulmonary drug disposition. Whilst the majority of reports present data from in vitro models, a growing number of publications advance the field by introducing sophisticated ex vivo and in vivo techniques. In a few cases, evidence from clinical studies in human volunteers is complementing the picture.

Areas covered: In this review, recent advances in pulmonary drug transporter research are critically evaluated. Transporter expression data in tissues and cell-based in vitro models is summarized and information on transport activity assessed. Novel techniques allowing for better quantification of transporter-related effects following pulmonary delivery are also described.

Expert opinion: Different tissue and cell populations of the lung have distinct transporter expression patterns. Whether these patterns are affected by disease, gender and smoking habits requires further clarification. Transporters have been found to have an impact on drug absorption processes, at least in vitro. Recent ex vivo experiments using isolated, perfused lung models, however, suggest that mainly efflux pumps have significant effects on absorption into the pulmonary circulation. Whether these rodent-based ex vivo models predict the human situation is basis for further research.

KEYWORDS:

• Drug transporters
• Pulmonary drug disposition
• P-glycoprotein
• MRP1
• Organic cation transporters
• Peptide transporters
• BCRP
• Inhalation

Article highlights.

• Transporter expression patterns are to be distinct in the various sections of the respiratory tract.

• Lung transporters can have an impact on drug absorption into the systemic circulation and on drug distribution into lung tissues.

• Transporters have shown to be associated with lung maladies such as COPD.

• Appropriate in vitro and ex vivo models can be used to predict transporter interactions and hence inform the drug development process.

This box summarizes key points contained in the article.

Declaration of interest

This work has been financially supported by a Clinical Investigator Awards from the Flight Attendant Medical Research Institute (FAMRI CIA 130016). M.A.S. is the recipient of a PhD bursary from the Iraqi Ministry of Higher Education and Scientific Research (MOHESR) and C.G.C. is supported by a Trinity College Research Studentship Award. The authors would like to acknowledge the contribution of the COST Actions BM1201 and MP1404. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.