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Co-delivery of doxorubicin and erlotinib through liposomal nanoparticles for glioblastoma tumor regression using an in vitro brain tumor model

Author:
Lakkadwala, Sushant, Singh, Jagdish
Source:
Colloids and surfaces 2019 v.173 pp. 27-35
ISSN:
0927-7765
Subject:
apoptosis, biocompatibility, blood-brain barrier, brain, brain neoplasms, colloids, cytotoxicity, doxorubicin, drug therapy, glioblastoma, hemolysis, models, nanoparticles, neoplasm cells, neuroglia, permeability, remission, transferrin
Abstract:
Glioma is a highly malignant tumor that starts in the glial cells of brain. Tumor cells reproduce quickly and infiltrate rapidly in high grade glioma. Permeability of chemotherapeutic agents into brain is restricted owing to the presence of blood brain barrier (BBB). In this study, we developed a dual functionalized liposomal delivery system for efficient transport of chemotherapeutics across BBB for the treatment of glioma. Liposomes were surface modified with transferrin (Tf) for receptor targeting, and cell penetrating peptide PFVYLI (PFV) to increase translocation of doxorubicin (Dox) and Erlotinib (Erlo) across the BBB into glioblastoma (U87) tumor cells. In vitro cytotoxicity and hemolysis studies were performed to assess biocompatibility of liposomal nanoparticles. Cellular uptake studies demonstrated efficient internalization of Dox and Erlo in U87, brain endothelial (bEnd.3), and glial cells. In addition, dual functionalized liposomes showed significantly (p < 0.05) higher apoptosis in U87 cells. Significantly (p < 0.05) higher translocation of dual functionalized liposomes across the BBB and delivering chemotherapeutic drugs to the glioblastoma tumor cells inside PLGA-Chitosan scaffold resulted in approximately 52% tumor cell death, using in vitro brain tumor model.
Agid:
6157206