Electrospun PMVEMA Nanofibers Developed as a Fast-Release Platform for Antineoplastic Drugs Tested in Glioblastoma Primary Cultures

<b>Background/Objectives</b>: The local release of antineoplastic drugs in post-surgical treatments is an alternative way to improve their effectiveness against glioblastoma reappearance. Thus, it was proposed to develop a local delivery system based on electrospun PMVEMA-derived nanofibers for the administration of carmustine (BCNU), temozolomide (TMZ), and doxorubicin (DOX). <b>Methods</b>: Electrospun nanofibers were prepared using PMVEMA-monoethyl ester (PMVEMA-Es) and PMVEMA-acid (PMVEMA-Ac), loading BCNU, TMZ, and DOX at 1% or 8% (<i>w</i>/<i>w</i>). Their morphology, encapsulation efficiency, and release profiles were characterized by FESEM, confocal microscopy, and HPLC. Their biological effects were evaluated through cell viability, cell cycle, and intracellular accumulation assays in established cell lines from glioblastoma patients (HGUE-GB) and human astrocytes (HAs). <b>Results</b>: The nanofibers were optimized without defects, and encapsulation efficiencies were above 80%. The release studies showed a rapid initial release in the first hour, being DOX > TMZ > BCNU, while the second release rate was sustained in the cases of PMVEMA-Ac/TMZ (0.14%/h) and PMVEMA-Es/BCNU (1.2%/h), highlighting that, after 24 h under physiological conditions, the degradation of the loaded drug was lower than its free state, comparable to the Gliadel release system. Furthermore, it was confirmed that there was a dose-dependent decrease in cell viability for PMVEMA-Es/BCNU and PMVEMA-Ac/DOX, with higher cytotoxicity than free DOX. Finally, the lowest concentration tested had a relatively low effect on HAs compared with its effect on glioblastoma cells. <b>Conclusion</b>: PMVEMA-based electrospun nanofibers are effective in encapsulating and releasing antineoplastic drugs, suggesting their potential as a local delivery system to improve glioblastoma post-surgical treatment efficacy.