Reinhardt, Luiza Steffens; Moras, Ana Moira; Henn, Jeferson Gustavo; Arantes, Pablo Ricardo; Ferro, Matheus Bernardes; Braganhol, Elizandra; de Souza, Priscila Oliveira; de Oliveira Merib, Josias; Borges, Gabriela Ramos; Dalanhol, Carolina Silveira; de Barros Dias, Mabilly Cox Holanda; Nugent, Michael; Moura, Dinara Jaqueline published the artcile< Nek1-inhibitor and temozolomide-loaded microfibers as a co-therapy strategy for glioblastoma treatment>, Reference of 112-63-0, the main research area is Drug delivery systems; Electrospinning; Glioblastoma; Microfibers; NIMA-related kinase 1; Polyvinyl alcohol; Temozolomide.
Malignant glioblastoma (GB) is the predominant primary brain tumor in adults, but despite the efforts towards novel therapies, the median survival of GB patients has not significantly improved in the last decades. Therefore, localised approaches that treat GB straight into the tumor site provide an alternative to enhance chemotherapy bioavailability and efficacy, reducing systemic toxicity. Likewise, the discovery of protein targets, such as the NIMA-related kinase 1 (Nek1), which was previously shown to be associated with temozolomide (TMZ) resistance in GB, has stimulated the clin. development of target therapy approaches to treat GB patients. In this study, we report an electrospun polyvinyl alc. (PVA) microfiber (MF) brain-implant prepared for the controlled release of Nek1 protein inhibitor (iNek1) and TMZ or TMZ-loaded nanoparticles. The formulations revealed adequate stability and drug loading, which prolonged the drugs′ release allowing a sustained exposure of the GB cells to the treatment and enhancing the drugs′ therapeutic effects. TMZ-loaded MF provided the highest concentration of TMZ within the brain of tumor-bearing rats, and it was statistically significant when compared to TMZ via i.p. (IP). All animals treated with either co-therapy formulation (TMZ + iNek1 MF or TMZ nanoparticles + iNek1 MF) survived until the endpoint (60 days), whereas the Blank MF (drug-unloaded), TMZ MF and TMZ IP-treated rats′ median survival was found to be 16, 31 and 25 days, resp. The tumor/brain area ratio of the rats implanted with either MF co-therapy was found to be reduced by 5-fold when compared to Blank MF-implanted rats. Taken together, our results strongly suggest that Nek1 is an important GB oncotarget and the inhibition of Nek1′s activity significantly decreases GB cells′ viability and tumor size when combined with TMZ treatment.
International Journal of Pharmaceutics (Amsterdam, Netherlands) published new progress about 112-63-0. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Reference of 112-63-0.
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