Journal
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
Volume 30, Issue -, Pages 435-442Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jddst.2015.08.004
Keywords
Osteosarcoma; Chemotherapy; Methotrexate; Edelfosine; Lipid nanoparticles; Lipid rafts
Categories
Funding
- Asociacion Espanola Contra el Cancer (AECC) [CI14142069BLAN]
- Convocatoria Ayudas Fundacion Caja Navarra
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Osteosarcoma (OS) is the most frequent primary malignant bone tumor in the pediatric population. Current treatments are not able to slow the progression of the disease in patients with metastasis, and their survival rate is still 10-30%. Therefore, new therapeutic approaches are required. In the last decades, lipid nanoparticles (LN) have been widely researched for cancer treatment. These systems are able to carry the cytostatic drug to the affected organs and control the release of their cargo in a prolonged manner. The purpose of the present study was to evaluate edelfosine efficacy in various primary osteosarcoma cell lines and a commercial cell line, and to compare its efficacy to that of methotrexate, a first-line agent traditionally employed in osteosarcoma therapy. We also studied whether the encapsulation of both drugs in LN, edelfosine and methotrexate, affected their in vitro efficacy. Methotrexate and edelfosine LN were successfully developed and characterized. Edelfosine showed higher efficacy treating the metastatic cells when compared to the primary cell lines due to its mechanism of entrance via lipid rafts. This efficacy was improved when edelfosine was administered in LN. Moreover, methotrexate showed higher efficacy in the cells that did not overexpress dihydrofolate reductase, the target enzyme of methotrexate. (C) 2015 Elsevier B.V. All rights reserved.
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