The Synergistic Effect of Co-delivery of Anticancer Drugs Into Astrocytes Isolated From Human Glioblastoma Multiforme

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.

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.

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.

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.