Liposomes are lipid bilayer nanovesicles that have inherent ability to deliver therapeutic and imaging agents to the tumor cells due to enhanced permeability and retention effect (EPR effect) and also by active targeting mechanism. The major hurdles in delivering the therapeutic agents to CNS malignancies are the blood-brain and blood-tumor barriers. Although several drugs are known to cross the blood brain barrier (BBB), they are not effective in eliminating the tumors completely. So a formulation that could enhance their ability to get across the BBB and actively targeting the tumor is necessary to overcome blood brain and blood tumor barrier. We have formulated variety of liposomes by varying the surface molecules and therapeutically active lipids. To determine the feasibility of the liposome formulation to cross the blood brain barrier we developed an in vitro blood brain barrier model using bovine brain microvascular endothelial cells (BBMVEC) cultured as monolayer. Various liposomal doxorubicin formulations were prepared after modifying their surface by protein conjugation, a small molecule inhibitor (farnesyl thiosalicylic acid), a small molecule iron chelator (Dp44mt) and glutathione. All the small molecules were chosen for this study rationally by in silico determination of the feasibility of the molecules to cross the BBB. Moreover, the liposomal doxorubicin was also rationally designed to mimimize the cardiotoxicity mediated by doxorubicin and to synergistically improve the therapeutic efficacy. In vitro cytotoxicity assays were performed in the glioma cell lines. BBB transport studies were performed after culturing bovine brain endothelial cells as monolayer in a transwell system. A time dependent increase in the transport of the compound occurs as evidenced by the in vitro BBB model. In vivo investigation reveals the transport of the targeted liposomes through the blood brain barrier after intravenous administration of the liposomes, as evidenced by fluorescent microscopic images of the mouse brain tissue.
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