Development of controlled-release cisplatin dry powders for inhalation against lung cancers

Vincent Levet, Rémi Rosière, Romain Merlos, Luca Fusaro, Gilles Berger, Karim Amighi, Nathalie Wauthoz

Résultats de recherche: Contribution à un journal/une revueArticleRevue par des pairs

Résumé

The present study focuses on the development of dry powders for inhalation as adjuvant chemotherapy in lung cancer treatment. Cisplatin was chosen as a potential candidate for a local treatment as it remains the main platinum component used in conventional chemotherapies, despite its high and cumulative systemic toxicities. Bulk cisplatin was reduced to submicron sizes using high-pressure homogenization, mixed with a solubilized lipid and/or PEGylated component and then spray-dried to produce controlled-release dry powder formulations. The obtained formulations were characterized for their physicochemical properties (particle size and morphology), aerodynamic performance and release profiles. Cisplatin content and integrity were assessed by electrothermal atomic absorption spectrometry and 195Pt nuclear magnetic resonance spectroscopy. DPI formulations with cisplatin contents ranging from 48.5 to 101.0% w/w exhibited high fine particle fractions ranging from 37.3% to 51.5% of the nominal dose. Formulations containing cisplatin microcrystals dispersed in solid lipid microparticles based on acceptable triglycerides for inhalation and PEGylated excipients showed a controlled-release for more than 24 h and a limited burst effect. These new formulations could provide an interesting approach to increasing and prolonging drug exposure in the lung while minimizing systemic toxicities.

langue originaleAnglais
Pages (de - à)209-220
Nombre de pages12
journalInternational Journal of Pharmaceutics
Volume515
Numéro de publication1-2
Les DOIs
Etat de la publicationPublié - 30 déc. 2016

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