Hydrolytic instability and low-loading levels of temozolomide to magnetic PLGA nanoparticles remain challenging against glioblastoma therapy

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dc.authoridŞentürk, Fatih/0000-0002-2436-3362
dc.authoridŞentürk, Fatih/0000-0002-2436-3362
dc.authoridÇakmak, Soner/0000-0003-2245-8322
dc.authorwosidŞentürk, Fatih/AEI-3613-2022
dc.authorwosidŞentürk, Fatih/HKE-0978-2023
dc.authorwosidÇakmak, Soner/I-4478-2015
dc.contributor.authorŞentürk, Fatih
dc.contributor.authorÇakmak, Soner
dc.contributor.authorGümüşderelioğlu, Menemse
dc.contributor.authorÖztürk, Göknur Güler
dc.date.accessioned2023-07-26T11:54:34Z
dc.date.available2023-07-26T11:54:34Z
dc.date.issued2022
dc.departmentDÜ, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Biyofizik Ana Bilim Dalıen_US
dc.description.abstractTemozolomide (TMZ) is the first-line chemotherapeutic agent for the treatment of newly diagnosed glioblastoma (GBM). However, chemoresistance, hydrolytic instability, and insufficient drug accumulation are major challenges limiting the effectiveness of TMZ chemotherapy. Although various nanocarriers have been offered to overcome these limitations, there are some discrepancies regarding the TMZ encapsulation efficiency (EE%). In this study, by examining the behavior of TMZ in different solvents, we aimed to confirm the loading efficiency of TMZ in the nanoparticles (NPs) and investigate the therapeutic efficacy of TMZ-loaded NPs in human GBM cell line (T98G). For this purpose, firstly, we investigated the stability of TMZ and its degradation product (AIC) to evaluate whether TMZ degradation affects the measured EE% from the supernatant (indirect method) or the NPs (direct method). Subsequently, we tried to load TMZ into magnetic poly (lactic-co-glycolic acid)-polyethylene glycol (PLGA-b-PEG) nanoparticles (TMZ-m-PNPs) by modifying the synthesis parameters in a controlled manner. It was concluded that the indirect method might cause misleading results due to the high hydrolytic instability of TMZ during the NPs synthesis or washing steps. Although many modifications have been performed in the synthesis method, the EE% of TMZ ranged between 1% and 7%. In cell culture, IC50 values of free-TMZ were found for human endothelial cells (HUVEC, similar to 500 mu M) and human glioblastoma cells (T98G, similar to 350 mu M) at the 72nd h. Furthermore, cell viability was quantified using MTT, live/dead cell viability, and Annexin V-FITC/PI assays of TMZ-m-PNPs, but cytotoxicity of NPs was not dose-dependent in T98G cells. Overall, this study offers two major new insights; first, the EE% of TMZ in NPs should be determined by the direct method; second, to increase the therapeutic efficacy of TMZ-loaded NPs on GBM cells, it may be recommended not to use the PLGA-based nanocarrier system that may contribute to poor therapeutic response.en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) [SBAG-118S027]; Cell and Tissue Engineering Research Group at Hacettepe Universityen_US
dc.description.sponsorshipThis study was supported by the Scientific and Technological Research Council of Turkey (TUBITAK), Grant no: SBAG-118S027. In addition, we are grateful for assistance of the Cell and Tissue Engineering Research Group at Hacettepe University. We are also thankful to Dr. Anil Sera Cakmak and Ozge Ekin Tuncay for their support in cell culture studies.en_US
dc.identifier.doi10.1016/j.jddst.2022.103101
dc.identifier.issn1773-2247
dc.identifier.issn2588-8943
dc.identifier.urihttps://doi.org/10.1016/j.jddst.2022.103101
dc.identifier.urihttps://hdl.handle.net/20.500.12684/12869
dc.identifier.volume68en_US
dc.identifier.wosWOS:000820166800008en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.institutionauthorŞentürk, Fatih
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.ispartofJournal of Drug Delivery Science and Technologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.snmz$2023V1Guncelleme$en_US
dc.subjectTemozolomide; Glioblastoma; Aic; Plga Nanoparticlesen_US
dc.subjectCentral-Nervous-System; Antitumor Efficacy; Stability; Cells; Inhibition; Expression; Deliveryen_US
dc.titleHydrolytic instability and low-loading levels of temozolomide to magnetic PLGA nanoparticles remain challenging against glioblastoma therapyen_US
dc.typeArticleen_US

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