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

Abstract

Abstract The effect of chemotherapy for anti-glioblastoma is limited due to insufficient drug delivery across the blood–brain–barrier. Poloxamer 188-coated nanoparticles can enhance the delivery of nanoparticles across the blood–brain–barrier. This study presents the design, preparation, and evaluation of a combination of PLGA nanoparticles (PLGA NPs) loaded with methotrexate (P-MTX NPs) and PLGA nanoparticles loaded with paclitaxel (P-PTX NPs), both of which were surface-modified with poloxamer188. Cranial tumors were induced by implanting 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 Ki-67 as a poor prognosis factor, was significantly lower in P-MTX NPs + P-PTX NPs compared to 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. The findings highlight the efficacy of combination nanochemotherapy in glioblastoma treatment, indicating the need for further preclinical studies.

Keywords

• Glioblastoma
• PLGA nanoparticle
• Poloxamer188
• Methotrexate
• Paclitaxel