Combinatorial chemotherapy via poloxamer 188 surface-modified PLGA nanoparticles that traverse the blood-brain-barrier in a glioblastoma model

Abstract

Abstract The effect of anti-glioblastoma therapies is dwindling due to insufficient delivery across the blood-brain-barrier. It has been stated that poloxamer 188-coated nanoparticles are able to circumvent the blood-brain-barrier. Building off of such success, this study presents the design, preparation, and evaluation of a combination of PLGA nanoparticles loaded with methotrexate (P-MTX NPs) and PLGA nanoparticles loaded with paclitaxel (P-PTX NPs) that were surface-modified by poloxamer188. Cranial tumors were implanted using C6 cells in a rat model and MRI demonstrated that the tumors were indistinguishable in the two rats with P-MTX NPs+P-PTX NPs treated groups. Brain PET scans exhibited a decreased brain-to-background ratio which could be attributed to the diminished metabolic tumor volume. The expression of p53 and Ki-67 as a good and poor prognosis factor, respectively were significantly more and less, in P-MTX NPs+P-PTX NPs than in the control. Furthermore, the biodistribution of PLGA NPs was determined by carbon quantum dots loaded into PLGA NPs (P-CQD NPs), and quantitative analysis of ex-vivo imaging of the dissected organs demonstrated that 17.2 ± 0.6 % of the NPs were concentrated in the brain after 48 h. These results demonstrate the promising combinatorial nano chemotherapy for the treatment of glioblastoma which needs to be urgently investigated in human clinical models.