Pulmonary Delivery of Peptides and Proteins

Cell lines of both airway and alveolar epithelial origin are available (immortal cells, transformed or carcinoma-derived), the most commonly used being the CALU-3 cell line derived from airway epithelium [37], and the A549 cell line derived from a bronchioalveolar carcinoma [38]. However, these cultured cell lines share only limited similarity in morphology, biochemical characteristics, and barrier properties (low epithelial resistance due to the lack of tight junctions) with the epithelia in vivo. Consequently, the results of absorption and metabolism studies based on cultured cell lines should be interpreted with caution. 

The primary cell culture model is a more valid model for the study of absorption and transport processes of a drug via the pulmonary route. It provides a tight epithelial barrier with morphological and functional properties resembling those of the in-vivo condition. Primary alveolar epithelial cells from rats [39], rabbits [40] and humans [41] which display morphological and biochemical characteristics similar to the native epithelium have been isolated and can be used for drug transport studies. 

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J. S. Patton and R. M. Platz, Routes of drug delivery case studies (2) pulmonary delivery of peptides and proteins for systemic action, Adv. Drug Deliv. Rev, 8, 179 (1992). 

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... 

In this chapter, we will discuss the biophysical basis and recent advances in pulmonary delivery of peptides and proteins. 

Wall, D.A. Smith, P.L. Inhalation therapy for growth hormone deficiency. In Inhalation Delivery of Therapeutic Peptides and Proteins Adjei, A.L., Gupta, P.R., Eds. Marcel Dekker, Inc. New York, 1997 453-469, Ch. 16. Patton, J.S. Platz, R.M. Routes of dehvery case studies (2) pulmonary delivery of peptides and proteins for systemic action. Adv. Drug Deh. Rev. 1992, 8, 179-186. 

Patton JS, Platz RM. Pulmonary delivery of peptides and proteins for systemie action. Adv Drug Deliv Rev 1992 8 179-196. 

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