title: Receptor-mediated endocytosis of macromolecules and strategy to enhance their transport in alveolar epithelial cells.
abstract: BACKGROUND
  Pulmonary delivery is an attractive administration route for therapeutic proteins and peptides. In this context, endocytosis/transcytosis at the distal lung epithelial barrier is an important process in the pulmonary absorption of therapeutic macromolecules. The alveolar epithelium is comprised of type I and type II cells. Understanding the transport mechanisms in these cells is essential for the development of efficient pulmonary delivery systems of therapeutic macromolecules.
  
  
  METHODS
  Endocytic pathways for albumin and insulin in alveolar epithelial cells and possible receptors for the endocytosis are discussed. Strategies to enhance the endocytosis and pulmonary absorption of macromolecules are also discussed, by focusing on the effects of cationic poly(amino acid)s.
  
  
  CONCLUSIONS
  Although the surface area occupied by type II cells in alveoli is much smaller than that covered by type I cells, type II cells may significantly contribute to the endocytosis/transcytosis of macromolecules such as albumin. Identification of the receptors involved in the cellular uptake of each macromolecule is prerequisite for the understanding and regulation of its transport into and across alveolar epithelial cells. Establishment of novel in-vitro culture cell models of type I and type II cells would be a great help for the future advance of this research field.
authors.affiliation: Hiroshima University, Graduate School of Biomedical and Health Sciences, Department of Pharmaceutics and Therapeutics , 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan +81 82 257 5315 ; +81 82 257 5319 ; takanom@hiroshima-u.ac.jp.
authors.forename: Mikihisa
authors.initials: M
authors.lastname: Takano
authors.forename: Masashi
authors.initials: M
authors.lastname: Kawami
authors.forename: Ayako
authors.initials: A
authors.lastname: Aoki
authors.forename: Ryoko
authors.initials: R
authors.lastname: Yumoto
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage* / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism
chemical_list: D007328:Insulin; D010455:Peptides
keywords: albumin; alveolar epithelial cells; cationic poly(amino acid)s; clathrin; endocytosis; endocytosis receptor; insulin; intracellular trafficking; megalin