Optimisation of pulmonary drug delivery of the model peptide drug, salmon calcitonin

Abstract

The use of the pulmonary route is a viable alternative administration route to injection, in particular for drugs with poor systemic bioavailability upon oral delivery such as therapeutic peptides and proteins. However, information about the expression and activity of metabolic enzymes (e.g., peptidases) on disposition of biopharmaceuticals after inhalation is critically missing. This information could help to better understand, if protective measures such as PEGylation, chemical modification or peptidase inhibitors are meaningful for pulmonary delivery of biotechnology medicines. It was the aim of this work to investigate the role of peptidases in pulmonary drug delivery of a model peptide drug, salmon calcitonin (sCT), and to find a suitable formulation for improved pulmonary drug delivery of this peptide. In a first step, mRNA expression levels of selected catabolising peptidases were determined in human lung epithelial cells. The proteolytic enzymes (i.e., carboxypeptidases; CPA1, CPA2, CPB, CPM; gamma-glutamyltransferases: GGT1,