Barriers to Pulmonary Absorption of Peptides and Proteins

Barriers to pulmonary absorption of proteins and peptides include respiratory mucus, mucociliary clearance, pulmonary enzymes/proteases, alveolar lining layer, alveolar epithelium, basement membrane, macrophages and other cells [3, 18]. The molecular weight cutoff of tight junctions for alveolar type I cells is 0.6 nm, while endothelial junctions allow the passage of larger molecules (4-6 nm). In order to reach the bloodstream in the endothelial vasculature, proteins and peptides must cross this alveolar epithelium, the capillary endothelium, and the intervening extracellular matrix. 

Alveolar epithelium and local proteases are believed to be the major barriers for the efficient absorption of inhaled proteins and peptides. Many novel and potent absorption enhancers have been investigated for the peptide/protein absorption 

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