Methotrexate-Loaded Chitosan- and Glycolchitosan-Based Nanoparticles: A Promising Strategy for the Administration of the Anticancer Drug to Brain Tumors

作者：Trapani Adriana^*; Denora Nunzio; Iacobellis Giuliano; Sitterberg Johannes; Bakowsky Udo; Kissel Thomas

来源：AAPS PHARMSCITECH, 2011, 12(4): 1302-1311.

DOI：10.1208/s12249-011-9695-x

• blood-brain barrier overcoming
• confocal microscopy
• glycol chitosan and chitosan nanoparticles
• P-glycoprotein
• Tween 80

Brain tumor treatment employing methotrexate (MTX) is limited by the efflux mechanism of Pg-p on the blood-brain barrier. We aimed to investigate MTX-loaded chitosan or glycol chitosan (GCS) nanoparticles (NPs) in the presence and in the absence of a coating layer of Tween 80 for brain delivery of MTX. The effect of a low Tween 80 concentration was evaluated. MTX NPs were formulated following the ionic gelation technique and size and zeta potential measurements were acquired. Transport across MDCKII-MDR1 monolayer and cytotoxicity studies against C6 glioma cell line were also performed. Cell/particles interaction was visualized by confocal microscopy. The particles were shown to be cytotoxic against C6 cells line and able to overcome MDCKII-MDR1 cell barrier. GCS-based NPs were the most cytotoxic NPs. Confocal observations highlighted the internalization of Tween 80-coated fluorescent NPs more than Tween 80-uncoated NPs. The results suggest that even a low concentration of Tween 80 is sufficient for enhancing the transport of MTX from the NPs across MDCKII-MDR1 cells. The nanocarriers represent a promising strategy for the administration of MTX to brain tumors which merits further investigations under in vivo conditions.

• 出版日期2011-12