Pharmacological Improvement and Preclinical Evaluation of Methotrexate-Loaded Lipid-Core Nanocapsules in a Glioblastoma Model
| Autor: | Adriana Raffin Pohlmann, de Oliveira Cp, Franciane Brackmann Mendes, S.S. Guterres, Elisa Helena Farias Jandrey, Ana Maria Oliveira Battastini, Fabrício Figueiró, Maria Isabel Albano Edelweiss, Liliana Rockenbach, Letícia Scussel Bergamin |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Antimetabolites Antineoplastic Cell Survival Biomedical Engineering Drug Evaluation Preclinical Pharmaceutical Science Medicine (miscellaneous) Bioengineering Pharmacology Flow cytometry Diffusion chemistry.chemical_compound Nanocapsules In vivo Glioma Cell Line Tumor Materials Testing medicine Animals General Materials Science MTT assay Viability assay Propidium iodide Particle Size Rats Wistar Tumor microenvironment medicine.diagnostic_test Brain Neoplasms Drug Synergism Cell cycle medicine.disease Rats Methotrexate Treatment Outcome chemistry Liposomes Glioblastoma |
| Zdroj: | Journal of biomedical nanotechnology. 11(10) |
| ISSN: | 1550-7033 |
| Popis: | Glioblastoma multiforme is a devastating cerebral tumor with an exceedingly poor prognosis. Methotrexate (MTX) is a folic acid analogue that inhibits DNA synthesis by binding to dihydrofolate reductase. Biodegradable nanoparticles are emerging as a promising system for drug delivery to specific tissues. The aims of the current study were pharmacological improvement and preclinical evaluation of MTX-loaded lipid-core nanocapsules (MTX-LNCs) in a glioblastoma model. Cell viability was assessed using the MTT assay, and the cell cycle was characterized by flow cytometry analysis of propidium iodide staining. Apoptosis was measured using an AnnexinV kit and by examining active caspase-3 immunocontent. In vivo glioma implantation was performed in rats, followed by measurement of the tumor size and tumoral apoptosis, BCL-2 immunohistochemistry and analyses of toxicological parameters. MTX-LNCs with increased encapsulation efficiency were successfully prepared. Our in vitro results showed a decrease in glioma cell viability after MTX-LNC treatment that was preceded by cell cycle arrest, leading the cells to undergo apoptotic death, as indicated by AnnexinV staining and increased active caspase-3 protein levels. In the in vivo glioma model, we observed a decrease in the tumor size and an increase in apoptosis in the tumor microenvironment (based on the AnnexinV assay and BCL-2 measurement). MTX-LNC treatment decreased the leukocyte number but altered neither toxicological tissue marker expression nor metabolic parameters. The present results reveal that MTX-LNCs represented an efficient formulation in a preclinical model of glioma and are a potential candidate for clinical trials. |
| Databáze: | OpenAIRE |
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