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Dioxadet-loaded nanogels as a potential formulation for glioblastoma treatment
Roman Voeikov,Tatiana Abakumova,Nadezhda Grinenko,Pavel Melnikov,Vladimir Bespalov,Alexander Stukov,Vladimir Chekhonin,Natalia Klyachko,Natalia Nukolova 한국약제학회 2017 Journal of Pharmaceutical Investigation Vol.47 No.1
Glioblastoma multiforme is a fast-growing malignant brain tumor with poor prognosis and low survival rate. Here we investigated the potential use of anticancer drug dioxadet loaded into nanogels for glioma treatment. We used block copolymer of polyethylene glycol and polymethacrylic acid for synthesis of dioxadet carriers and two types of cross-linking agents: non-degradable ethylenediamine and biodegradable cystamine, containing disulfide bond. We analyzed physicochemical properties of nanoparticles, their loading capacity, cytotoxicity of drug-loaded nanogels, and also their internalization into glioma cells. We found the optimal conditions that promote the efficient loading of the drug. We demonstrated that dioxadet loaded nanogels have relatively high level of loading capacity (>35% w/w) and loading efficiency (>75%). We shown that nanogels with the biodegradable cross-links prone to dissociate under reducing conditions (glutathione) that allow to decrease IC50 values of the drug compared to the nanogels with ethylendiamine cross-links. This stimuli-sensitive behavior of nanogels could be beneficial for tumor treatment. Confocal analysis of glioma cells demonstrated that both types of nanogels accumulate in cells and localize in lysosomes. These results indicate that loading of dioxadet into nanoparticles can improve its performance; such formulation has a potential for further studies and practical applications.
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