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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Main Authors: Joanna Kuźmińska, Agnieszka Sobczak, Aleksandra Majchrzak-Celińska, Izabela Żółnowska, Aleksandra Gostyńska, Barbara Jadach, Violetta Krajka-Kuźniak, Anna Jelińska, Maciej Stawny
Format: Article
Language:English
Published: MDPI AG 2023-08-01
Series:Pharmaceutics
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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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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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