Thursday, September 27, 2018

PLGA from PolySciTech used in development of blood-brain-barrier penetrating nanoparticle-based treatment of brain cancer


Brain cancer is often deadly and very difficult to treat partially due to the presence of the blood-brain-barrier, which prevents medicine from crossing over into the brain cavity. One means of delivering drug into this region is to generate small particles bearing specific signaling moieties such as transferrin or cell-penetrating peptide which triggers the endothelial lining of the brain to allow the particles to pass. Recently, researchers at North Dakota State University used PLGA (Polyvivo AP022) from PolySciTech (www.polyscitech.com) as part of their development of custom liposomal nanoparticles to deliver chemotherapeutic agents across the blood-brain-barrier. This research holds promise for improved therapies for brain-cancer in the future. Read More: Lakkadwala, Sushant, and Jagdish Singh. "Co-delivery of Doxorubicin and Erlotinib through Liposomal Nanoparticles for Glioblastoma Tumor Regression Using an In Vitro Brain Tumor Model." Colloids and Surfaces B: Biointerfaces (2018). https://www.sciencedirect.com/science/article/pii/S0927776518306581

“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. Highlights: 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. Keywords: Dual-functionalized liposomes Glioblastoma In vitro brain tumor model Co-delivery Blood brain barrier”
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