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AuthorFatemeh, Madani
AuthorEsnaashari, Seyedeh Sara
AuthorBergonzi, Maria Camilla
AuthorWebster, Thomas J.
AuthorYounes, Husam M.
AuthorKhosravani, Masood
AuthorAdabi, Mahdi
Available date2023-06-21T08:07:39Z
Publication Date2020-09-01
Publication NameLife Sciences
Identifierhttp://dx.doi.org/10.1016/j.lfs.2020.117943
ISSN00243205
URIhttps://www.sciencedirect.com/science/article/pii/S0024320520306937
URIhttp://hdl.handle.net/10576/44644
AbstractAimThe aim of this study was to improve the therapeutic index of chemotherapeutic drugs on glioblastoma cells through an improved co-drug delivery system. Materials and methodsMethotrexate (MTX) and paclitaxel (PTX) were co-loaded into poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) coated with polyvinyl alcohol (PVA) and Poloxamer188 (P188). Key findingsThe mean size of the NPs was about 212 nm, with a zeta potential of about −15.7 mV. Encapsulation efficiency (EE%) and drug loading (DL%) were determined to be 72% and 4% for MTX and 85% and 4.9% for PTX, respectively. The prepared NPs were characterized by differential thermal analysis (DTA) and thermogravimetric analysis (TGA). Moreover, an in vitro sustained release profile was observed for both drug loaded PLGA NPs. Glioblastoma cellular uptake of the NPs was confirmed by fluorescence microscopy and cell survival rate was investigated through the 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method after 48 h of incubation showing IC50 values of 24.5 μg·mL−1 for PTX and 9.5 μg·mL−1 for MTX for the MTX/PTX co-loaded PLGA nanoparticles coated with PVA/P188 (Co-2 NPs). Apoptosis and necrosis were also studied via flow cytometry, the lactate dehydrogenase (LDH) assay and the amount of anti-apoptotic protein (Bcl-2) expression. Blood compatibility of the co-delivery of PTX and MTX loaded PLGA NPs was investigated using a hemolysis method as well. SignificanceThe co-delivery of PTX and MTX loaded PLGA NPs is promising for the treatment of glioblastoma compared to their respective free drug formulations and, thus, should be further investigated.
SponsorThis work was supported by Tehran University of Medical Sciences, Grant No. 96-01-87-34138, Iran.
Languageen
PublisherElsevier
SubjectPaclitaxel
Methotrexate
PLGA
Co-delivery
Glioblastoma
Nanoparticles
TitlePaclitaxel/methotrexate co-loaded PLGA nanoparticles in glioblastoma treatment: Formulation development and in vitro antitumor activity evaluation
TypeArticle
Volume Number256
dc.accessType Open Access


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