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Local and systemic pharmacokinetic evaluation of immediate-release and controlled-release cisplatin dry powders for inhalation against lung cancer

par Levet, Vincent ;Rosiere, Rémi ;Amighi, Karim ;Wauthoz, Nathalie
Référence Drug delivery to the lungs (27: December 6-9th 2016: Edinburgh, Scotland)
Publication Non publié, 2016-12-06

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Résumé :

Cisplatin is the major component of the IV doublet chemotherapy regimen to combat lung cancer. However it exerts very high toxicities (i.e.nephrotoxicity, ototoxicity, myelosupression). Inhaled cisplatin chemotherapy could lower them by increasing local concentration in the lungs near the tumor site while decreasing the acute and chronic exposure in non-targeted organs. To limit local toxicity and optimize the tumor exposure, drug release after deposition of high cisplatin doses in the lungs should be controlled. Therefore, we developed dry powders for inhalation including solid lipid microparticles (SLMs) with controlled release properties with or without PEGylated excipients (F3, F4 and F2, respectively) [1] to modulate their clearance by alveolar macrophages. Therefore the aim of the study was to evaluate the platinum pharmacokinetic of these controlled-release formulations in comparison to a dry powder for inhalation with immediate-release (F1) and cisplatin solution by endotracheal nebulization (EN) and intravenous (IV) route.