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Development of Doxorubicin-Loaded Magnetic Silica-Pluronic F-127 Nanocarriers Conjugated with Transferrin for Treating Glioblastoma across the Blood-Brain Barrier Using an in Vitro Model.

ACS omega (2018-08-09)
Geetha B Heggannavar, Chinmay G Hiremath, Divya D Achari, Vishwas G Pangarkar, Mahadevappa Y Kariduraganavar
ABSTRACT

Brain glioma is the most lethal type of cancer, with extremely poor prognosis and high relapse. Unfortunately, the treatment of brain glioma is often limited because of the low permeability of anticancer drugs across the blood-brain barrier (BBB). To circumvent this, magnetic mesoporous nanoparticles were synthesized and loaded with doxorubicin as an anticancer agent. These nanoparticles were fabricated with Pluronic F-127 and subsequently conjugated with transferrin (Tf) to achieve the sustained release of the drug at the targeted site. The physicochemical properties of the conjugated nanoparticles were analyzed using different techniques. The magnetic saturation of the nanoparticles determined by a vibration sample magnetometer was found to be 26.10 emu/g. The cytotoxicity study was performed using the MTT assay at 48 and 96 h against the U87 cell line. The Tf-conjugated nanoparticles (DOX-MNP-MSN-PF-127-Tf) exhibited a significant IC50 value (0.570 μg/mL) as compared to the blank nanoparticles (121.98 μg/mL). To understand the transport mechanism of drugs across the BBB, an in vitro BBB model using human brain microvascular endothelial cells was developed. Among the nanoparticles, the Tf-conjugated nanoparticles demonstrated an excellent permeability across the BBB. This effect was predominant in the presence of an external magnetic field, suggesting that magnetic particles present in the matrix facilitated the uptake of drugs in U87 cells. Finally, it is concluded that nanoparticles conjugated with Tf effectively crossed the BBB. Thus, the developed nanocarriers can be considered as potential candidates to treat brain tumor.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Tetraethyl orthosilicate, reagent grade, 98%
Sigma-Aldrich
N-Hydroxysuccinimide, 98%