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Iranian Journal of Medical Physics، جلد ۱۵، شماره Special Issue-۱۲th. Iranian Congress of Medical Physics، صفحات ۱۳۵-۱۳۵
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عنوان انگلیسی Formulation of temozolomide by folic acid-conjugated tri-block copolymer nanoparticles for targeted drug delivery
چکیده انگلیسی مقاله Introduction: Glioblastoma multiforme (GBM) is the most frequent primary malignant tumor of the brain. But, the treatment of GBM is one of the most problems in cancer therapy because of poor drug penetration across the blood-brain barrier (BBB). Targeting drug delivery system and conjugating targeting moieties was recognized to overcome the poor penetration of chemotherapy drugs into tumor cells. In the present study, folic acid- conjugated magnetite tri-block copolymer was utilized to targeted chemotherapy of the glioma cells. Materials and Methods: The characterization and morphology of NPs (SPION-PEG-PBA- PEG, SPION-PEG-PBA-PEG-FA, TMZ-SPION-PEG-PBA-PEG, and TMZ-SPION-PEG-PBA-PEG- FA) were determined by Dynamic Light Scattering (DLS) analysis and transmission electron microscope (TEM). The in vitro release behaviors of TMZ from NPs were evaluated with an equilibrium dialysis bag diffusion method. Additionally, to identify the targeting effect of FA- conjugated NPs, C6 glioblastoma cells and OLN-93 glial cells were used. The cytotoxicity effect of NPs was determined by the MTT assays in both cell lines. Results: DLS analysis showed that all nanoparticles had mean diameters of 24-49 nm. In our study, TMZ entrapment efficiency of TMZ-SPION-PEG-PBA-PEG-FA and TMZ-SPION-PEG- PBA-PEG nanoparticles were 52.8 and 50%, respectively, with the drug loading capacity of 6.65 and 6.3%, respectively. It was found that nearly 90% of TMZ in stock solution was released within the first 2 h. However, TMZ-loaded NPs generated only 75% leakage within the 48 h and revealed a sustained release feature, which might be described by that drug was gradually released with the dissolution of polymers. The results from the MTT assay indicated that TMZ-SPION-PEG-PBA-PEG-FA NPs revealed the highest anti-proliferation effect on the C6 cells compared with OLN-93 cells (P < 0.0001). Also, compared with unmodified NPs, conjugation with FA-ligand could further elevate the cytotoxicity effect on C6 cells (P < 0.0001) which demonstrated a satisfactory drug delivery system. Conclusion: TMZ-SPION-PEG-PBA-PEG-FA NPs served as a potential system for the transport of TMZ across the GBM cells through receptor-mediated endocytosis. The results revealed that proposed system could be exploited as potential carrier for delivery of drugs to the brain.
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نویسندگان مقاله | Soraya Emamgholizadeh Minaei
Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.


| Samideh Khoei
Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. . E-mail: khoei.s@iums.ac.ir, Tel: +98 9125468630 Razi Drug Research Centre, Iran University of Medical Sciences, Tehran, Iran


| Sepideh Khoee
Department of Polymer Chemistry, School of Sciences, University of Tehran, Tehran, Iran


| Sakine shirvalilou
Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
نشانی اینترنتی http://ijmp.mums.ac.ir/article_12629.html
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