TY - JOUR
T1 - Development and characterization of a temozolomide-loaded nanoemulsion and the effect of ferrocene pre and co-treatments in glioblastoma cell models
AU - Henn, Jeferson Gustavo
AU - Bernardes Ferro, Matheus
AU - Lopes Alves, Gabriel Antonio
AU - Pires Peña, Flávia
AU - de Oliveira, João Vitor Raupp
AU - de Souza, Bárbara Müller
AU - da Silva, Leonardo Fonseca
AU - Rapack Jacinto Silva, Victória
AU - Silva Pinheiro, Ana Carolina
AU - Steffens Reinhardt, Luiza
AU - Morás, Ana Moira
AU - Nugent, Michael
AU - da Rosa, Ricardo Gomes
AU - Silveira Aguirre, Tanira Alessandra
AU - Moura, Dinara Jaqueline
N1 - Publisher Copyright:
© 2023, The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.
PY - 2023/12
Y1 - 2023/12
N2 - Background: Glioblastoma is a severe brain tumor that requires aggressive treatment involving surgery, radiotherapy, and chemotherapy, offering a survival rate of only 15 months. Fortunately, recent nanotechnology progress has enabled novel approaches and, alongside ferrocenes’ unique properties of cytotoxicity, sensitization, and interaction with reactive oxygen species, have brought new possibilities to complement chemotherapy in nanocarrier systems, enhancing treatment results. Methods: In this work, we developed and characterized a temozolomide-loaded nanoemulsion and evaluated its cytotoxic potential in combination with ferrocene in the temozolomide-resistant T98G and temozolomide-sensitive U87 cell lines. The effects of the treatments were assessed through acute assays of cell viability, cell death, mitochondrial alterations, and a treatment protocol simulation based on different two-cycle regimens. Results: Temozolomide nanoemulsion showed a z-average diameter of 173.37 ± 0.86 nm and a zeta potential of – 6.53 ± 1.13 mV. Physicochemical characterization revealed that temozolomide is probably associated with nanoemulsion droplets instead of being entrapped within the nanostructure, allowing a rapid drug release. In combination with ferrocene, temozolomide nanoemulsion reduced glioblastoma cell viability in both acute and two-cycle regimen assays. The combined treatment approach also reversed T98G’s temozolomide-resistant profile by altering the mitochondrial membrane potential of the cells, thus increasing reactive oxygen species generation, and ultimately inducing cell death. Conclusions: Altogether, our results indicate that using nanoemulsion containing temozolomide in combination with ferrocene is an effective approach to improve glioblastoma therapy outcomes. Graphical abstract: [Figure not available: see fulltext.]
AB - Background: Glioblastoma is a severe brain tumor that requires aggressive treatment involving surgery, radiotherapy, and chemotherapy, offering a survival rate of only 15 months. Fortunately, recent nanotechnology progress has enabled novel approaches and, alongside ferrocenes’ unique properties of cytotoxicity, sensitization, and interaction with reactive oxygen species, have brought new possibilities to complement chemotherapy in nanocarrier systems, enhancing treatment results. Methods: In this work, we developed and characterized a temozolomide-loaded nanoemulsion and evaluated its cytotoxic potential in combination with ferrocene in the temozolomide-resistant T98G and temozolomide-sensitive U87 cell lines. The effects of the treatments were assessed through acute assays of cell viability, cell death, mitochondrial alterations, and a treatment protocol simulation based on different two-cycle regimens. Results: Temozolomide nanoemulsion showed a z-average diameter of 173.37 ± 0.86 nm and a zeta potential of – 6.53 ± 1.13 mV. Physicochemical characterization revealed that temozolomide is probably associated with nanoemulsion droplets instead of being entrapped within the nanostructure, allowing a rapid drug release. In combination with ferrocene, temozolomide nanoemulsion reduced glioblastoma cell viability in both acute and two-cycle regimen assays. The combined treatment approach also reversed T98G’s temozolomide-resistant profile by altering the mitochondrial membrane potential of the cells, thus increasing reactive oxygen species generation, and ultimately inducing cell death. Conclusions: Altogether, our results indicate that using nanoemulsion containing temozolomide in combination with ferrocene is an effective approach to improve glioblastoma therapy outcomes. Graphical abstract: [Figure not available: see fulltext.]
KW - Drug delivery system
KW - Ferrocene
KW - Glioblastoma
KW - Nanoemulsion
KW - Temozolomide
UR - http://www.scopus.com/inward/record.url?scp=85174141533&partnerID=8YFLogxK
U2 - 10.1007/s43440-023-00537-6
DO - 10.1007/s43440-023-00537-6
M3 - Article
C2 - 37837521
AN - SCOPUS:85174141533
SN - 1734-1140
VL - 75
SP - 1597
EP - 1609
JO - Pharmacological Reports
JF - Pharmacological Reports
IS - 6
ER -