Pulmonary protein absorption

Type I pneumocytes make up most of the epithelial surface. It is the large, thin, type I pneumocytes that are the primary site of pulmonary protein absorption. The type II pneumocytes, lying in niches between type I cells, are the main source of surfactants and also replace type I cells as they undergo apoptosis (programmed cell death) after about 120 days. 

Mechanisms of Protein Absorption after Pulmonary Delivery... 

Hussain, A., J J. Arnold, M.A. Khan, and F. Ahsan. 2004. Absorption enhancers in pulmonary protein delivery. J. Control. Release 94 15-24. 

Possible noninvasive routes for delivery of proteins include nasal, buccal, rectal, vaginal, transdermal, ocular, oral, and pulmonary. For each route of delivery there are two potential barriers to absorption permeability and enzymatic barriers. All of the... 

A higher concentration of red blood cells, total protein and leukotriene B4 has been measured in the lungs of athletes during severe exercise (i.e. high levels of pulmonary capillary pressures) compared to controls, indicating an altered integrity of the air-to-blood barrier [155]. In addition, an increased absorption rate and plasma Cmax of inhaled terbutaline during submaximal... 

Wall DA (1995) Pulmonary absorption of peptides and proteins. Drug Debv 2 1-20. 

Systemic absorption of pulmonary-deUvered peptides and proteins has been the objective of many investigations [2]. The most successful work in this field is the development of insulin formulations for inhalation.These dosage forms might, in the near future, become a suitable alternative for the current subcutaneous injection of insulin that is used to obtain meal-time glucose control [3]. In spite of the strict requirements regarding dose variability for insulin, the pulmonary products under development seem to be as safe as the subcutaneous injections. 

Many studies have been carried out regarding the absorption of peptides and proteins after pulmonary drug dehvery. The perspectives of a non-parenteral route of administration for larger proteins led to studies on the pulmonary absorption of proteins of different size. To date, over 30 different proteins have been evaluated with regard to absorption rate and... 

Table 3.2. Absorption data after pulmonary administration of peptides and proteins. Data from reference [32].

Several pharmaceutical and physiological barriers must be overcome for the successful pulmonary delivery of peptide and protein drugs [3], For example, many of these macromolecular drugs have relatively low permeability when they are administered without any absorption enhancers [4], Furthermore, the clinical toxicology of peptides/proteins in the lung, especially for chronic disease, should be of some concern [6], Therefore, cost-benefit ratios should be evaluated in the... 

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. 

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