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

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2019-01, Vol.173, p.27-35
• Main Authors: Lakkadwala, Sushant, Singh, Jagdish
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Biological Transport; Blood brain barrier; Blood-Brain Barrier - metabolism; Brain - drug effects; Brain - metabolism; Brain - pathology; Brain Neoplasms - blood supply; Brain Neoplasms - drug therapy; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Cell Line, Tumor; Cell-Penetrating Peptides - chemistry; Cell-Penetrating Peptides - metabolism; Chitosan - chemistry; Co-delivery; Doxorubicin - chemistry; Doxorubicin - pharmacology; Drug Delivery Systems - methods; Dual-functionalized liposomes; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Endothelial Cells - pathology; Erlotinib Hydrochloride - chemistry; Erlotinib Hydrochloride - pharmacology; Glioblastoma; Glioblastoma - blood supply; Glioblastoma - drug therapy; Glioblastoma - metabolism; Glioblastoma - pathology; Humans; In vitro brain tumor model; Liposomes - chemistry; Liposomes - metabolism; Models, Biological; Neuroglia - drug effects; Neuroglia - metabolism; Neuroglia - pathology; Polylactic Acid-Polyglycolic Acid Copolymer - chemistry; Protein Binding; Receptors, Transferrin - metabolism; Tissue Scaffolds; Transferrin - chemistry; Transferrin - metabolism
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2018.09.047

[Display omitted] •Transferrin-PFVYLI (Tf-PFV) liposomes were prepared by post-insertion method.•Tf-PFV liposomes showed Tf receptor targeting and enhanced cell penetration.•Cytotoxicity and hemolysis studies exhibited biocompatibility of the liposomes.•Increased transport of Tf-PFV liposomes across the barrier into tumor-scaffold.•Tf-PFV liposomes demonstrated excellent anti-tumor efficacy. 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