Delivery of doxorubicin to glioblastoma multiforme in vitro using solid lipid nanoparticles with surface aprotinin and melanotransferrin antibody for enhanced chemotherapy

• DPPC of 40% (w/w) in lipids is appropriate to fabricate Apr-Anti-MTf-Dox-SLNs.
• Apr-Anti-MTf-Dox-SLNs can prevent Dox from burst release.
• Apr-Anti-MTf-Dox-SLNs do not induce a serious cytotoxicity to HBMECs and HAs.
• Apr-Anti-MTf-Dox-SLNs enhance the ability of Dox to infuse the BBB.
• Apr-Anti-MTf-Dox-SLNs inhibit the growth of GBM.

Solid lipid nanoparticles (SLNs) conjugated with aprotinin (Apr) and melanotransferrin antibody (Anti-MTf) were used to carry doxorubicin (Dox) across the blood–brain barrier (BBB) for glioblastoma multiforme (GBM) chemotherapy. Dox-entrapped SLNs with grafted Apr and Anti-MTf (Apr-Anti-MTf-Dox-SLNs) were applied to a cellular monolayer comprising human brain-microvascular endothelial cells (HBMECs) with a regulation of human astrocyte (HAs) and to a proliferated colony of U87MG cells. Based on the average particle diameter, zeta potential, entrapping efficiency of Dox, and grafting efficiency of Apr and Anti-MTf, we found that 1,2-dipalmitoyl-sn-glycero-3-phosphocholine of 40% (w/w) in lipids was appropriate for fabricating Apr-Anti-MTf-Dox-SLNs. In addition, Apr-Anti-MTf-Dox-SLNs could prevent Dox from fast dissolution and did not induce a serious cytotoxicity to HBMECs and HAs when compared with free Dox. Moreover, the treatment with Apr-Anti-MTf-Dox-SLNs enhanced the ability of Dox to infuse the BBB and to inhibit the growth of GBM. The current Apr-Anti-MTf-Dox-SLNs can be a promising pharmacotherapeutic preparation to penetrate the BBB for malignant brain tumor management.

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