In vivo assessment of temozolomide local delivery for lung cancer inhalation therapy
Autor: | Sven Saussez, Robert Kiss, Véronique Mathieu, Christine Decaestecker, Philippe Deleuze, Julien Hecq, Karim Amighi, Isabelle Roland, Olivier Debeir, Ivan Adanja, Nathalie Wauthoz |
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Jazyk: | angličtina |
Rok vydání: | 2010 |
Předmět: |
Pathology
medicine.medical_specialty Lung Neoplasms Melanoma Experimental Pharmaceutical Science Antineoplastic Agents Pharmacology Lung pseudo-metastases NSCLC Mice In vivo Cell Line Tumor Administration Inhalation medicine Temozolomide Distribution (pharmacology) Animals Particle Size Lung cancer Fluorescent microparticles Chromatography High Pressure Liquid Fluorescent Dyes Aerosol therapy Inhalation business.industry Melanoma Cancer Reproducibility of Results Sciences bio-médicales et agricoles medicine.disease Dacarbazine Drug delivery Female Mouse B16F10 melanoma business medicine.drug |
Zdroj: | European journal of pharmaceutical sciences, 39 |
Popis: | The aim of this study was to compare the efficacy of local drug delivery by inhalation to intravenous delivery in a B16F10 melanoma metastatic lung model. Temozolomide was formulated as a suspension, which was elaborated and evaluated in terms of particle size, shape and agglomeration. An endotracheal administration device was used to aerosolise the suspension. This mode of delivery was evaluated at different temozolomide concentrations and was optimized for the uniformity of delivered dose, the droplet size distribution and the distribution of droplets in vivo. Of the particles in the stabilised suspension, 79% were compatible with the human respirable size range, and this formulation retained 100% in vitro anticancer activity as compared to temozolomide alone in three distinct cancer cell lines. The pulmonary delivery device provided good reproducibility in terms of both the dose delivered and the droplet size distribution. Most of the lung tissues that were exposed to aerosol droplets contained the particles, as revealed by fluorescent microscopy techniques. The global in vivo antitumour activity of the inhaled temozolomide provided a median survival period similar to that for intravenous temozolomide delivery, and three out of 27 mice (11%) survived with almost complete eradication of the lung tumours. The present study thus shows that inhalation of a simple liquid formulation is well tolerated and active against a very biologically aggressive mouse melanoma pulmonary pseudo-metastatic model. This inhalation delivery could be used to deliver other types of anticancer drugs. JOURNAL ARTICLE info:eu-repo/semantics/published |
Databáze: | OpenAIRE |
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