Journal
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 143, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ejps.2019.105183
Keywords
Electrospinning; Dacarbazine; Nanofibers; Polyvinyl alcohol; Glioblastoma
Categories
Funding
- Government of Ireland International Education Scholarship (GOI-IES)
- Athlone Institute of Technology research and development funding
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazil (CAPES)
- Programa Pesquisa para o SUS (PPSUS) [17/2551-0001388-3]
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Malignant glioblastoma (GB) treatment consists of resection surgery followed by radiotherapy and chemotherapy (CT). Despite several implications, such as systemic toxicity and low efficacy, CT continues to be used for GB therapy. Aiming to overcome the blood-brain barrier (BBB) limitations, one of the most promising approaches is the use of drug delivery systems (DDS) to treat the cancer cells in situ. Dacarbazine (DTIC) is an antitumor agent that has limited application given its high toxicity to healthy cells. However, it is effective against GB recurrent cells. In this study, DTIC polymeric nanofibers (NF) were successfully prepared, characterized and its in vitro anticancer efficacy was determined. This system demonstrated high drug loading of 83.9 +/- 6.5%, good stability and mechanical properties and sustained drug release, improved in tumor pH (6.8). This controlled release prolonged the uptake of GB improving DTIC antitumor effects such as DNA damage and cell death by apoptosis. Molecular dynamics simulations revealed that DTIC interacts with PVA, possibly explaining the controlled release of the drug. Therefore, DTIC NF brain-implants show great potential as a promising drug delivery system for GB therapy.
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