Etoricoxib-Cannabidiol Combo: Potential Role in Glioblastoma Treatment and Development of PLGA-Based Nanoparticles
Background: Glioblastoma (GBM) is the most frequently occurring primary malignant central nervous system tumor, with a poor prognosis and median survival below two years. Administration of a combination of non-steroidal anti-inflammatory drugs and natural compounds that exhibit a curative or prophyl...
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MDPI AG
2023-08-01
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Online Access: | https://www.mdpi.com/1999-4923/15/8/2104 |
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author | Joanna Kuźmińska Agnieszka Sobczak Aleksandra Majchrzak-Celińska Izabela Żółnowska Aleksandra Gostyńska Barbara Jadach Violetta Krajka-Kuźniak Anna Jelińska Maciej Stawny |
author_facet | Joanna Kuźmińska Agnieszka Sobczak Aleksandra Majchrzak-Celińska Izabela Żółnowska Aleksandra Gostyńska Barbara Jadach Violetta Krajka-Kuźniak Anna Jelińska Maciej Stawny |
author_sort | Joanna Kuźmińska |
collection | DOAJ |
description | Background: Glioblastoma (GBM) is the most frequently occurring primary malignant central nervous system tumor, with a poor prognosis and median survival below two years. Administration of a combination of non-steroidal anti-inflammatory drugs and natural compounds that exhibit a curative or prophylactic effect in cancer is a new approach to GBM treatment. This study aimed to investigate the synergistic antitumor activity of etoricoxib (ETO) and cannabidiol (CBD) in a GBM cell line model, and to develop poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) for these two substances. Methods: The activity of ETO+CBD was determined using the MTT test, cell-cycle distribution assay, and apoptosis analysis using two GBM cell lines, namely, T98G and U-138 MG. The PLGA-based NPs were developed using the emulsification and solvent evaporation method. Their physicochemical properties, such as shape, size, entrapment efficiency (EE%), in vitro drug release, and quality attributes, were determined using scanning electron microscopy, diffraction light scattering, high-performance liquid chromatography, infrared spectroscopy, and differential scanning calorimetry. Results: The combination of ETO and CBD reduced the viability of cells in a dose-dependent manner and induced apoptosis in both tested GBM cell lines. The developed method allowed for the preparation of ETO+CBD-NPs with a spherical shape, mean particle size (MPS) below 400 nm, zeta potential (ZP) values from −11 to −17.4 mV, polydispersity index (PDI) values in the range from 0.029 to 0.256, and sufficient EE% of both drugs (78.43% for CBD, 10.94% for ETO). Conclusions: The combination of ETO and CBD is a promising adjuvant therapeutic in the treatment of GBM, and the prepared ETO+CBD-NPs exhibit a high potential for further pharmaceutical formulation development. |
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institution | Directory Open Access Journal |
issn | 1999-4923 |
language | English |
last_indexed | 2024-03-10T23:39:55Z |
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spelling | doaj.art-c9eb5df67286417a98ed42eeebe594c22023-11-19T02:36:52ZengMDPI AGPharmaceutics1999-49232023-08-01158210410.3390/pharmaceutics15082104Etoricoxib-Cannabidiol Combo: Potential Role in Glioblastoma Treatment and Development of PLGA-Based NanoparticlesJoanna Kuźmińska0Agnieszka Sobczak1Aleksandra Majchrzak-Celińska2Izabela Żółnowska3Aleksandra Gostyńska4Barbara Jadach5Violetta Krajka-Kuźniak6Anna Jelińska7Maciej Stawny8Chair and Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, PolandChair and Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, PolandChair and Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Święcickiego 4, 60-781 Poznań, PolandChair and Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, PolandChair and Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, PolandChair and Department of Pharmaceutical Technology, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, PolandChair and Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Święcickiego 4, 60-781 Poznań, PolandChair and Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, PolandChair and Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, PolandBackground: Glioblastoma (GBM) is the most frequently occurring primary malignant central nervous system tumor, with a poor prognosis and median survival below two years. Administration of a combination of non-steroidal anti-inflammatory drugs and natural compounds that exhibit a curative or prophylactic effect in cancer is a new approach to GBM treatment. This study aimed to investigate the synergistic antitumor activity of etoricoxib (ETO) and cannabidiol (CBD) in a GBM cell line model, and to develop poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) for these two substances. Methods: The activity of ETO+CBD was determined using the MTT test, cell-cycle distribution assay, and apoptosis analysis using two GBM cell lines, namely, T98G and U-138 MG. The PLGA-based NPs were developed using the emulsification and solvent evaporation method. Their physicochemical properties, such as shape, size, entrapment efficiency (EE%), in vitro drug release, and quality attributes, were determined using scanning electron microscopy, diffraction light scattering, high-performance liquid chromatography, infrared spectroscopy, and differential scanning calorimetry. Results: The combination of ETO and CBD reduced the viability of cells in a dose-dependent manner and induced apoptosis in both tested GBM cell lines. The developed method allowed for the preparation of ETO+CBD-NPs with a spherical shape, mean particle size (MPS) below 400 nm, zeta potential (ZP) values from −11 to −17.4 mV, polydispersity index (PDI) values in the range from 0.029 to 0.256, and sufficient EE% of both drugs (78.43% for CBD, 10.94% for ETO). Conclusions: The combination of ETO and CBD is a promising adjuvant therapeutic in the treatment of GBM, and the prepared ETO+CBD-NPs exhibit a high potential for further pharmaceutical formulation development.https://www.mdpi.com/1999-4923/15/8/2104etoricoxibcannabidiolglioblastomaPLGAnanocarriersdrug nanoformulations |
spellingShingle | Joanna Kuźmińska Agnieszka Sobczak Aleksandra Majchrzak-Celińska Izabela Żółnowska Aleksandra Gostyńska Barbara Jadach Violetta Krajka-Kuźniak Anna Jelińska Maciej Stawny Etoricoxib-Cannabidiol Combo: Potential Role in Glioblastoma Treatment and Development of PLGA-Based Nanoparticles Pharmaceutics etoricoxib cannabidiol glioblastoma PLGA nanocarriers drug nanoformulations |
title | Etoricoxib-Cannabidiol Combo: Potential Role in Glioblastoma Treatment and Development of PLGA-Based Nanoparticles |
title_full | Etoricoxib-Cannabidiol Combo: Potential Role in Glioblastoma Treatment and Development of PLGA-Based Nanoparticles |
title_fullStr | Etoricoxib-Cannabidiol Combo: Potential Role in Glioblastoma Treatment and Development of PLGA-Based Nanoparticles |
title_full_unstemmed | Etoricoxib-Cannabidiol Combo: Potential Role in Glioblastoma Treatment and Development of PLGA-Based Nanoparticles |
title_short | Etoricoxib-Cannabidiol Combo: Potential Role in Glioblastoma Treatment and Development of PLGA-Based Nanoparticles |
title_sort | etoricoxib cannabidiol combo potential role in glioblastoma treatment and development of plga based nanoparticles |
topic | etoricoxib cannabidiol glioblastoma PLGA nanocarriers drug nanoformulations |
url | https://www.mdpi.com/1999-4923/15/8/2104 |
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