Abstract
Background: Chemotherapy drugs are not effective in the treatment of primary brain tumors due to the low efficacy of these drugs and drug transfer from the blood-brain barrier (BBB) toward the tumor site. Our purpose in this study was to assess the co-delivery of anticancer drugs to increase drug permeability from BBB.Methods: In this study, two chemotherapy drugs, namely methotrexate (MTX) and paclitaxel (PTX), were inserted into polyvinyl alcohol and poloxamer188-conjugated nanoparticles (NPs). Astrocytes were treated with different concentrations of 0-50 μg/ml from MTX, PTX, the MTX-PTX mixture, PTX-loaded NPs, MTX-loaded NPs, and PTX-MTX co-loaded NPs for 48 hours. The tumoricidal effect was assessed using the survival rate, Hoechst staining, and western blotting.Results: The results indicated significant reduction of the survival rate in astrocytes treated with PTX-MTX co-loaded NPs. In addition, apoptosis hallmarks consisting of fragmented DNA, overexpression of Bax, and expression reduction of Bcl-2 were in the cultured astrocytes.Conclusions: Our study proposes that the PTX-MTX co-delivery to NPs could be used as a possible approach for anti-cancer drug delivery to glioblastoma multiforme.
Highlights
Glioblastoma multiforme is the most aggressive and deadliest of malignant brain cancers in humans
The astrocytes were cultured in DMEM/F12 medium consisting of 1% (100 U/mL) antibiotic/antimycotic and 2% fetal bovine serum (FBS) and maintained in an incubator
Cell Rate Survival The astrocytes were isolated from human glioblastoma tissue and treated with different drugs after 14 days (Figure 1)
Summary
Glioblastoma multiforme is the most aggressive and deadliest of malignant brain cancers in humans. Glioblastoma can grow very fast and spread quickly into the surrounding normal brain This property causes tumor recurrence and decreases the patient survival rate. The median survival rate of patients was reported to be 15 months after prognosis.[1] Despite the advancement of chemotherapy drugs for growth inhibition of cancer cells, drug entrance into the brain is restricted due to the blood-brain barrier (BBB) structure.[2] To overcome this problem, studies have indicated that nanotechnology can help chemotherapy in drug delivery from BBB and increase chemotherapy efficacy through drug transfer to brain tumor cells. Methods: In this study, two chemotherapy drugs, namely methotrexate (MTX) and paclitaxel (PTX), were inserted into polyvinyl alcohol and poloxamer188-conjugated nanoparticles (NPs).
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