Direct lung delivery of a dry powder formulation of DTPA with improved aerosolization properties: effect on lung and systemic decorporation of plutonium.
J Control Release
; 118(1): 78-86, 2007 Mar 12.
Article
en En
| MEDLINE
| ID: mdl-17241685
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 mum 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 PuO(2), a 3-fold increase of the Pu urinary excretion was observed, but the dissolution of PuO(2) in the lungs was not enhanced.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Quelantes
/
Plutonio
/
Aerosoles
/
Ácido Pentético
/
Pulmón
Límite:
Animals
Idioma:
En
Revista:
J Control Release
Asunto de la revista:
FARMACOLOGIA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Países Bajos