1: Am J Physiol Lung Cell Mol Physiol.  2004 May;286(5):L1002-8. Epub 2003 Dec
24. 

Alveolar macrophages are a primary barrier to pulmonary absorption of
macromolecules.

Lombry C, Edwards DA, Preat V, Vanbever R.

Dept. of Pharmaceutical Technology, School of Pharmacy, Universite Catholique de
Louvain, Ave. E. Mounier 73 UCL 73.20, 1200 Brussels, Belgium.
vanbever@farg.ucl.ac.be

We demonstrate that a primary source of elimination of inhaled macromolecules
after delivery to the lungs and before absorption into the systemic circulation
owes to clearance by alveolar macrophages (AM). Depletion of AM by
liposome-encapsulated dichloromethylene diphosphonate is shown to cause
severalfold enhancement in systemic absorption of IgG and human chorionic
gonadotropin after intratracheal instillation in rats. Lowering the doses of IgG
delivered to the lungs alleviates local degradation and results in a dramatic
increase in systemic absorption of the protein as well. Chemical and physical
means of minimizing uptake of macromolecules by AM are proposed as novel methods
for enhancing protein absorption from the lungs. Such strategies may have
important ramifications on the development of inhalation as an attractive mode
of administration of therapeutic proteins to the bloodstream.

PMID: 14695119 [PubMed - in process]