Development of controlled-release cisplatin dry powders for inhalation against lung cancers
| Autor: | Romain Merlos, Gilles Berger, Rémi Rosiere, Luca Fusaro, Nathalie Wauthoz, Karim Amighi, Vincent Levet |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Lung Neoplasms
Lung cancer chemotherapy Controlled-release Chemistry Pharmaceutical Drug Compounding Pharmaceutical Science chemistry.chemical_element 02 engineering and technology law.invention Polyethylene Glycols Solid lipid microparticles Excipients 03 medical and health sciences 0302 clinical medicine law Administration Inhalation medicine Desiccation Particle Size Pulmonary delivery Lung cancer Cisplatin Chromatography Inhalation Chemistry Dry Powder Inhalers 021001 nanoscience & nanotechnology medicine.disease Controlled release Dry-powder inhaler Dry powder inhaler Solubility 030220 oncology & carcinogenesis Delayed-Action Preparations Particle size Powders 0210 nano-technology Atomic absorption spectroscopy Platinum medicine.drug |
| Zdroj: | International Journal of Pharmaceutics. 515(1-2):209-220 |
| ISSN: | 1873-3476 0378-5173 |
| DOI: | 10.1016/j.ijpharm.2016.10.019 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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