Ducreux, Julie
[UCL]
Vanbever, Rita
Background: Recently, our laboratory demonstrated that alveolar macrophages (AM) comprised a major "barrier" to the transport of macromolecules from the lungs into the bloodstream, particulary for moderate‑sized to large proteins. Depletion of AM by liposomes-encapsulated clodronate induced a several-fold enhancement in the systemic absorption of IgG (150 kDa) and human chorionic gonadotropin (39.5 kDa) after intratracheal instillation in rats. Objective: The objective of this work was to study the role of AM in alveolar clearance of human growth hormone (hGH). Methods: AM of rats were depleted using intratracheal instillation of liposomes‑encapsulated Cl2MDP or clodronate. Intratracheal instillation of PBS-liposomes suspension was used as control. Forty-eight hours after pulmonary delivery of PBS- or Cl2MDP-liposomes suspension or PBS, rats were intratracheally instilled with hGH in solution. Rats received 600 µg/kg of hGH by intratracheal instillation or 100 µg/kg of hGH by IV injection for calculation of absolute bioavailability. A total of 12 blood samples were collected from jugular veins over 4h (IV injection) or 7h (Intratracheal instillation). The hGH plasma concentrations were measured using an ELISA assay. Results: Depletion of AM by liposomes-encapsulated clodronate did not enhance the systemic absorption of hGH after intratracheal instillation in rats. Conclusion: This study showed that AM were not a significant mechanism of clearance of hGH following pulmonary delivery. The lower molecular weight of hGH as compared to IgG and human chorionic gonadotropin involves a faster transport across the alveolar epithelium, from the airspace into the bloodstream, and a shorter residence time within alveoli that does not permit significant uptake by AM.
Bibliographic reference |
Ducreux, Julie ; Vanbever, Rita. Assessment of alveolar macrophages role in growth hormone pulmonary fate.Annual Meeting & Exposition of the Controlled Release Society (Vienne, du 22/07/2006 au 26/07/2006). |
Permanent URL |
http://hdl.handle.net/2078.1/138789 |