Using catanionic solid lipid nanoparticles with wheat germ agglutinin and lactoferrin for targeted delivery of etoposide to glioblastoma multiforme

Abstract

Abstract Catanionic solid lipid nanoparticles (CASLNs) with surface wheat germ agglutinin (WGA) and lactoferrin (Lf) were formulated to entrap and release etoposide (ETP), cross the blood–brain barrier (BBB), and inhibit glioblastoma multiforme (GBM) growth. Microemulsified ETP-CASLNs were modified with WGA and Lf to permeate a cultured monolayer of human brain-microvascular endothelial cells (HBMECs) regulated by human astrocytes and to treat malignant U87MG cells. Experimental evidence revealed that an increase in the weight percentage of ETP from 1% to 4% decreased its encapsulation efficiency about 34-44%. In addition, the release rate of ETP from WGA-Lf-ETP-CASLNs decreased with an increase in the concentration of catanionic surfactant from 7.5 µM to 12.5 µM, and WGA-Lf-ETP-CASLNs at 12.5 µM of catanionic surfactant exhibited a feature of sustained release. WGA-Lf-ETP-CASLNs also reduced transendothelial electrical resistance from 245.5 Ω×cm 2 to 191.5 Ω×cm 2 , enhanced the permeability of propidium iodide from 3.62×10 −6 cm/s to 5.61×10 −6 cm/s, induced a minor cytotoxicity to HBMECs, increased the ability of ETP to cross the BBB by about 5.6 times, and improved the antiproliferative efficacy of U87MG cells. The grafting of WGA and Lf is crucial to control the medicinal property of ETP-CASLNs, and WGA-Lf-ETP-CASLNs can be promising colloidal carriers in GBM management.