SHalabalija, Dushko
Preferred name
SHalabalija, Dushko
Official Name
SHalabalija, Dushko
Main Affiliation
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Item type:Publication, Radiosensitizing properties of dual-functionalized carbon nanostructures loaded with temozolomide(Beilstein Institut, 2025-02-19); ; ; In the present study, temozolomide (TMZ), a drug used for the treatment of anaplastic astrocytoma and glioblastoma multiforme (GBM), was incorporated into multiwalled carbon nanotubes (MWCNTs) and a MWCNTs–graphene (MWCNTs-G) hybrid compound, covalently functionalized with polyethylene glycol (PEG) 6000 and folic acid (FA), with an aim to prepare nanocarriers with the potential to prolong the drug circulation time, cross the blood–brain–tumor barrier (BBTB), and provide targeted and controlled drug release in the brain tumor cells. Cytotoxicity and effects on cell membrane integrity of the blank and TMZ-loaded dual-functionalized carbon nanostructures (CNs) were evaluated in vitro on a GBM cell line (U87MG), as well as their radiosensitizing properties after exposure of the pre-treated GBM cells to gamma radiation with a standard clinical dose for patients with GBM. All prepared formulations underwent biopharmaceutical and physicochemical characterization, including the formulations exposed to irradiation under the same conditions. For physicochemical characterization of the formulations, different techniques were used by which successful functionalization of the CNs and TMZ loading were confirmed and visualized; no significant changes in the structure of the CNs and TMZ after irradiation were observed. With single and dual functionalization, formulations with relatively high TMZ loading efficiency and drug content were prepared. They exhibited homogeneous particle size distributions and mean particle sizes and surface charges suitable for crossing the BBTB and targeting brain cancer cells. A biphasic drug release profile was observed for all functionalized TMZ-loaded formulations in simulated in vivo conditions, with a sustained release pointing to the potential for controlled release of TMZ in brain tumor cells. The formulations of the hybrid CN MWCNTs-G compared to the corresponding MWCNTs were characterized by a similar or slightly higher TMZ content, larger particle size, similar surface charge, and slightly faster TMZ release, which can be attributed to the planar structure of graphene that promotes TMZ binding to the surface on a larger scale. For the irradiated CNs, lower values for particle size, more positive values for surface charge, and accelerated TMZ release were observed, which could be explained by changes in the physicochemical characteristics of the prepared formulations upon irradiation. Significant concentration-dependent toxicity was observed for blank dual-functionalized CNs, being higher for MWCNTs-G-PEG6000-FA compared to MWCNTs-PEG6000-FA at the same formulation concentrations. With incorporation of TMZ into the functionalized CNs, the cell viability additionally decreased, maintaining the trend for higher cytotoxicity of the hybrid CN. Additional decrease in the viability of cells was observed when GBM cells pre-treated with the corresponding CNs were exposed to irradiation, which could be ascribed to changes in size, surface charge, and release kinetics of TMZ and to irradiation-induced changes in the microenvironment and cell membranes that promote uptake of a larger volume of carriers in the GBM cells. The higher cytotoxicity observed in the hybrid carrier formulations could most likely be attributed to the length of the hybrid carrier and the higher proportion of planar surface, which promotes more intense contact with the cells and rupture of cell membranes. Overall, the findings demonstrate the radiosensitizing properties of not only TMZ but also of CNs and point to a clinical benefit from combined treatment with carbon nanocarriers of TMZ and radiotherapy in GBM. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, THE EFFECTS OF COENZYME Q10 MICELLAR SOLUTION AND NANOLIPOSOMES ON SUPEROXIDE DISMUTASE (SOD) ACTIVITY IN CISPLATIN-INDUCED OXIDATIVE STRESS IN RATS(SHMSHM - AAMD, 2023); ; ; Introduction: CoenzymeQ10 (CoQ10) is a lipid-soluble antioxidant that plays a key role in the mitochondria respiratory chain in the synthesis of adenosine triphosphate (ATP). It combats the oxidative stress in the body via increasing endogenous cellular defense system represented by superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) activity. Cisplatin is an antineoplastic drug used for treatment of various human malignances but because of its cytotoxicity, the therapeutic outcome of this drug is limited. Namely, it causes oxidative stress in the body by reducing the levels for glutathione (GSH), SOD, GpX, CAT and GR. Therefore, the aim of this study was to evaluate the influence of the CoQ10 supplementation (in a form of micellar solution or encapsulated into nanoliposomes) on SOD activity in oxidative stress, induced by the treatment with Cisplatin on rats. Materials and methods: 90 normotensive Wistar rats (250-300 g) were included in this study. The animals were divided in 6 groups, each consisting of 15 rats. Cisplatin (5 mg/kg) and different formulations/combinations with CoQ10 (micellar solution or nanoliposomes dispersion, 10 mg/kg) were administrated i.p. After 12 days, both kidneys were removed for measuring of SOD activity in the tissue. SOD activity was determined by the autoxidation of pyrogallol spectrophotometrically at 420 nm. Statistical analysis was performed using Statistica 7.1 for Windows. Significance was determined at p<0.05 Results: CoQ10 nanoliposome treated group showed significantly increased SOD activity, compared to all other five groups. CoQ10 nanoliposome/Cisplatin treated group showed significantly increased SOD activity compared to the Cisplatin group. Additionally, CoQ10/Cisplatin group showed increased kidney SOD activity, compared to the Cisplatin group. Conclusion: According to these results, CoQ10, as a potent antioxidant and encapsulated into nanoliposomes could be one of the possible solutions to reduce the oxidative stress and nephrotoxicity caused by the cisplatin treatment as a side effect, which is a common reason for reducing or discontinuing therapy. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Influence of surface characteristics on the in vitro stability and cell uptake of nanoliposomes for brain delivery(Beilstein Institut, 2026-01-13); ; ;