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

Abstract：

: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 24h 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.

journal_name

Int J Pharm

journal_title

International journal of pharmaceutics

authors

Levet V,Rosière R,Merlos R,Fusaro L,Berger G,Amighi K,Wauthoz N

doi

10.1016/j.ijpharm.2016.10.019

subject

Has Abstract

pub_date

2016-12-30 00:00:00

pages

209-220

issue

1-2

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(16)30953-X

journal_volume

515

pub_type

杂志文章

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