1. Combination chemotherapy via poloxamer 188 surface-modified PLGA nanoparticles that traverse the blood-brain-barrier in a glioblastoma model.
- Author
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Madani F, Morovvati H, Webster TJ, Najaf Asaadi S, Rezayat SM, Hadjighassem M, Khosravani M, and Adabi M
- Subjects
- Animals, Rats, Cell Line, Tumor, Paclitaxel administration & dosage, Paclitaxel pharmacology, Paclitaxel chemistry, Paclitaxel pharmacokinetics, Paclitaxel therapeutic use, Tissue Distribution, Drug Carriers chemistry, Male, Drug Delivery Systems, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Humans, Glioblastoma drug therapy, Glioblastoma pathology, Glioblastoma metabolism, Glioblastoma diagnostic imaging, Polylactic Acid-Polyglycolic Acid Copolymer chemistry, Blood-Brain Barrier metabolism, Blood-Brain Barrier drug effects, Nanoparticles chemistry, Poloxamer chemistry, Methotrexate chemistry, Methotrexate administration & dosage, Methotrexate pharmacology, Brain Neoplasms drug therapy, Brain Neoplasms pathology, Brain Neoplasms diagnostic imaging, Brain Neoplasms metabolism
- 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., (© 2024. The Author(s).)
- Published
- 2024
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