Nanocomposite formulation for a sustained release of free drug and drug-loaded responsive nanoparticles: an approach for a local therapy of glioblastoma multiforme.
Autor: | Erthal LCS; School of Pharmacy and Pharmaceutical Sciences and Trinity St. James's Cancer Institute, Panoz Institute, Trinity College Dublin, College Green, Dublin 2, Ireland., Shi Y; Department of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic, Forckenbeckstrasse 55, 52074, Aachen, Germany., Sweeney KJ; National Neurosurgical Centre, Beaumont Hospital, Dublin 9, Ireland.; Royal College of Surgeons in Ireland, Dublin 2, Ireland., Gobbo OL; School of Pharmacy and Pharmaceutical Sciences and Trinity St. James's Cancer Institute, Panoz Institute, Trinity College Dublin, College Green, Dublin 2, Ireland., Ruiz-Hernandez E; School of Pharmacy and Pharmaceutical Sciences and Trinity St. James's Cancer Institute, Panoz Institute, Trinity College Dublin, College Green, Dublin 2, Ireland. ruizhere@tcd.ie. |
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Jazyk: | angličtina |
Zdroj: | Scientific reports [Sci Rep] 2023 Mar 29; Vol. 13 (1), pp. 5094. Date of Electronic Publication: 2023 Mar 29. |
DOI: | 10.1038/s41598-023-32257-5 |
Abstrakt: | 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. (© 2023. The Author(s).) |
Databáze: | MEDLINE |
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