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Nanocomposite formulation for a sustained release of free drug and drug-loaded responsive nanoparticles: an approach for a local therapy of glioblastoma multiforme

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posted on 2023-04-24, 16:20 authored by Luiza C S Erthal, Yang Shi, Kieron SweeneyKieron Sweeney, Oliviero L Gobbo, Eduardo Ruiz-Hernández

Malignant gliomas are a type of primary brain tumour that originates in glial cells. Among them, glioblastoma multiforme (GBM) is the most common and the most aggressive brain tumour in adults, classified as grade IV by the World Health Organization. The standard care for GBM, known as the Stupp protocol includes surgical resection followed by oral chemotherapy with temozolomide (TMZ). This treatment option provides a median survival prognosis of only 16-18 months to patients mainly due to tumour recurrence. Therefore, enhanced treatment options are urgently needed for this disease. Here we show the development, characterization, and in vitro and in vivo evaluation of a new composite material for local therapy of GBM post-surgery. We developed responsive nanoparticles that were loaded with paclitaxel (PTX), and that showed penetration in 3D spheroids and cell internalization. These nanoparticles were found to be cytotoxic in 2D (U-87 cells) and 3D (U-87 spheroids) models of GBM. The incorporation of these nanoparticles into a hydrogel facilitates their sustained release in time. Moreover, the formulation of this hydrogel containing PTX-loaded responsive nanoparticles and free TMZ was able to delay tumour recurrence in vivo after resection surgery. Therefore, our formulation represents a promising approach to develop combined local therapies against GBM using injectable hydrogels containing nanoparticles. 

Funding

European Research Council under Grant Agreement No 758887 (REACT)

European Union’s Horizon 2020 Research and Innovation programme under Grant Agreement No 952259 (NANOFACTS)

Wellcome Trust Institutional Strategic Support Fund

Postgraduate Ussher Fellowship from School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin

History

Comments

The original article is available at https://www.nature.com/

Published Citation

Erthal LCS, Shi Y, Sweeney KJ, Gobbo OL, Ruiz-Hernandez E. Nanocomposite formulation for a sustained release of free drug and drug-loaded responsive nanoparticles: an approach for a local therapy of glioblastoma multiforme. Sci Rep. 2023;13(1):5094.

Publication Date

29 March 2023

PubMed ID

36991081

Department/Unit

  • Beaumont Hospital
  • Surgery

Publisher

Nature Publishing Group,

Version

  • Published Version (Version of Record)