Direct lung delivery of a dry powder formulation of DTPA with improved aerosolization properties: effect on lung and systemic decorporation of plutonium

Autor: Jean-Robert Deverre, P. Fritsch, Henri Benech, Elias Fattal, C. Gervelas, A. L. Sérandour, B. Le Gall, Sandrine Geiger, Nicolas Tsapis, C. Taulelle, G. Grillon
Přispěvatelé: Laboratoire Structures, Propriétés et Modélisation des solides (SPMS), Institut de Chimie du CNRS (INC)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2006
Předmět:
Male
medicine.medical_specialty
Chemistry
Pharmaceutical
Pharmaceutical Science
chemistry.chemical_element
02 engineering and technology
030226 pharmacology & pharmacy
Rats
Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Drug Stability
X-Ray Diffraction
Administration
Inhalation
medicine
Animals
Chelation
Particle Size
Lung
Aerosolization
Chelating Agents
Aerosols
Inhalation
Radiochemistry
[CHIM.MATE]Chemical Sciences/Material chemistry
Pentetic Acid
021001 nanoscience & nanotechnology
Plutonium
Surgery
Rats
Ammonium bicarbonate
medicine.anatomical_structure
chemistry
Spray drying
Microscopy
Electron
Scanning
[PHYS.PHYS.PHYS-CHEM-PH]Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph]
Particle size
Powders
0210 nano-technology
Porosity
Zdroj: Journal of Controlled Release
Journal of Controlled Release, Elsevier, 2007, 118 (1), pp.78-86. ⟨10.1016/j.jconrel.2006.11.027⟩
ISSN: 0168-3659
DOI: 10.1016/j.jconrel.2006.11.027⟩
Popis: International audience; DTPA, an actinide chelating agent, has demonstrated its ability to complex plutonium (Pu) and to facilitate its urinary excretion after internal contamination. This process, known as decorporation is crucial to diminish the burden of Pu in the body. The ability to deliver a chelating agent directly to the alveolar region may increase its local concentration as compared to systemic delivery and therefore increase the extent of decorporation. Second, inhalation offers the potential for needle-free, systemic delivery of small molecules and would be convenient in case of nuclear accident as a first pass emergency treatment. To benefit from the improvement of inhalation technology, we have formulated DTPA into porous particles by spray-drying with dl-Leucine, DPPC and ammonium bicarbonate. The optimized particles possess a volume mean geometric diameter around 4.5 μm and crumpled paper morphology. The in vitro aerodynamic evaluation shows that about 56% of the powder should deposits in the lungs, with about 27% in the alveolar region, an improvement as compared with the micronized powder available with the Spinhaler®. After pulmonary administration to rats contaminated with PuO2, a 3-fold increase of the Pu urinary excretion was observed, but the dissolution of PuO2 in the lungs was not enhanced.
Databáze: OpenAIRE
Externí odkaz: