Abstract
In this study, we investigated the effects of temozolomide (TMZ)/Poly (lactide-co-glycolide)(PLGA)/nano-hydroxyapatite microspheres on the behavior of U87 glioma cells. The microspheres were fabricated by the “Solid/Water/Oil” method, and they were characterized by using X-Ray diffraction, scanning electron microscopy and differential scanning calorimetry. The proliferation, apoptosis and invasion of glioma cells were evaluated by MTT, flow cytometry assay and Transwell assay. The presence of the key invasive gene, αVβ3 integrin, was detected by the RT-PCR and Western blot method. It was found that the temozolomide/PLGA/nano-hydroxyapatite microspheres have a significantly diminished initial burst of drug release, compared to the TMZ laden PLGA microspheres. Our results suggest they can significantly inhibit the proliferation and invasion of glioma cells, and induce their apoptosis. Additionally, αVβ3 integrin was also reduced by the microspheres. These data suggest that by inhibiting the biological behavior of glioma cells in vitro, the newly designed temozolomide/PLGA/nano-hydroxyapatite microspheres, as controlled drug release carriers, have promising potential in treating glioma.
Highlights
Glioblastoma, the most common type of primary brain tumor, is considered to be one of the most severe forms of human cancer
The results revealed that different morphologies of nHA had been prepared successfully, and the morphologies of the spherical nHA and rod-like nHA were consistent with our previous study [19]
The affinity between the drug molecule and nHA mainly depends on the morphology of the nanoparticles [18], with stronger drug adhesion strength observed with the spherical nHA than with the rod-like nHA
Summary
Glioblastoma, the most common type of primary brain tumor, is considered to be one of the most severe forms of human cancer. HA is a major component of bone, exhibiting good biocompatibility It has been widely investigated as a drug carrier for the delivery of various pharmaceutical molecules due to its biocompatible, nontoxic, and non-inflammatory properties [12,13]. Many research groups have demonstrated that incorporation of nHA into PLGA microspheres could enhance the encapsulation efficacy (EE) of the drugs and prolong the duration of release [15,16,17]. Most of these studies were limited to the evolution of the drug (or protein)/PLGA/nHA controlled release system. We further explored the mechanism of the effect of TMZ/PLGA/nHA microspheres on U87 glioma cells
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