Enhanced delivery of etoposide across the blood-brain barrier to restrain brain tumor growth using melanotransferrin antibody- and tamoxifen-conjugated solid lipid nanoparticles

Journal of Drug Targeting
Yung-Chih Kuo, I-Hsin Wang

Abstract

Melanotransferrin antibody (MA) and tamoxifen (TX) were conjugated on etoposide (ETP)-entrapped solid lipid nanoparticles (ETP-SLNs) to target the blood-brain barrier (BBB) and glioblastom multiforme (GBM). MA- and TX-conjugated ETP-SLNs (MA-TX-ETP-SLNs) were used to infiltrate the BBB comprising a monolayer of human astrocyte-regulated human brain-microvascular endothelial cells (HBMECs) and to restrain the proliferation of malignant U87MG cells. TX-grafted ETP-SLNs (TX-ETP-SLNs) significantly enhanced the BBB permeability coefficient for ETP and raised the fluorescent intensity of calcein-AM when compared with ETP-SLNs. In addition, surface MA could increase the BBB permeability coefficient for ETP about twofold. The viability of HBMECs was higher than 86%, suggesting a high biocompatibility of MA-TX-ETP-SLNs. Moreover, the efficiency in antiproliferation against U87MG cells was in the order of MA-TX-ETP-SLNs  >  TX-ETP-SLNs  >  ETP-SLNs  >  SLNs. The capability of MA-TX-ETP-SLNs to target HBMECs and U87MG cells during internalization was verified by immunochemical staining of expressed melanotransferrin. MA-TX-ETP-SLNs can be a potent pharmacotherapy to deliver ETP across the BBB to GBM.

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Citations

Dec 26, 2016·Toxicological Sciences : an Official Journal of the Society of Toxicology·Liecheng YangLeshuai W Zhang
Jan 20, 2017·CNS Drugs·Mayur M Patel, Bhoomika M Patel
Feb 1, 2020·Expert Opinion on Therapeutic Patents·Rishi PaliwalMukesh Kumar Sahu
Jun 12, 2020·Expert Opinion on Drug Delivery·Suchada NiamsuphapChristopher B Howard
Jun 7, 2021·International Journal of Pharmaceutics·Marcela Tavares LuizMarlus Chorilli
Aug 29, 2021·Pharmaceutics·Mantosh Kumar SatapathyChih-Hao Yang

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