Anti-melanotransferrin and apolipoprotein E on doxorubicin-loaded cationic solid lipid nanoparticles for pharmacotherapy of glioblastoma multiforme

Abstract

Abstract Cationic solid lipid nanoparticles (CSLNs) with surface anti-melanotransferrin (AMT) and apolipoprotein E (ApoE) were used to carry antimitotic doxorubicin (Dox) across the blood–brain barrier (BBB) for glioblastoma multiforme (GBM) treatment. Dox-loaded CSLNs (Dox-CSLNs) were prepared in microemulsion, grafted covalently with AMT and ApoE, and applied to human brain-microvascular endothelial cells (HBMECs), human astrocytes, and U87MG cells. An increase in the weight percentage of stearylamine (SA) and a decrease in the stirring rate enhanced the particle size and the absolute value of the zeta potential of AMT-ApoE-Dox-CSLNs. In addition, the encapsulation efficiency of Dox in CSLNs decreased with increases in the weight percentage of Dox and the order in the encapsulation efficiency of Dox was 10% SA > 20% SA > 0% SA. However, the reverse order was true for the release rate of Dox, suggesting that AMT-ApoE-Dox-CSLNs containing 10% SA had better characteristics of sustained release. Moreover, AMT-ApoE-Dox-CSLNs fabricated at 10 µg/mL of ApoE could slightly reduce the transendothelial electrical resistance and increase the permeability of propidium iodide. AMT-ApoE-Dox-CSLNs did not induce serious cytotoxicity to HBMECs, and AMT-ApoE-Dox-CSLNs fabricated at 10 µg/mL of AMT and at 5–10 µg/mL of ApoE could significantly enhance the permeability of Dox across the BBB. The order in the efficacy of inhibiting U87MG cells was AMT-ApoE-Dox-CSLNs > AMT-Dox-CSLNs > Dox-CSLNs > Dox. Hence, AMT-ApoE-Dox-CSLNs have appropriate physicochemical properties and can be a potential colloidal delivery system for brain tumor chemotherapy.