Cationized Albumin Conjugated Solid Lipid Nanoparticles as Vectors for Brain Delivery of an Anti-Cancer Drug

Abhinav      Agarwal; Saikat      Majumder; Himanshu      Agrawal; Subrata      Majumdar; Govind      P. Agrawal

doi:10.2174/157341311794480291

Abstract

The present study investigates the prospective of surface engineered solid lipid nanoparticles as vectors to bypass BBB and provide improved therapeutic efficacy of encapsulated anti-cancer drug Methotrexate (MTX). MTX loaded SLNs were prepared and conjugated with cationic bovine serum albumin (CBSA). Ligand conjugated and unconjugated formulations were characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, particle size/polydispersity index and zeta-potential analysis. In vitro, the SLNs exhibited a biphasic pattern illustrated by an initial rapid release followed by rather sustained release profile of the drug. Furthermore, hemolytic studies elucidated the formulations to be biocompatible when compared to MTX. Transendothelial transport study on brain capillary endothelial cells (BCs) depicted CBSA conjugated SLNs to undergo transcytosis to a greatest extent. These SLNs were preferably taken up by BCs and Human neuroglial culture (HNGC)-1 tumor cells as evaluated against unconjugated SLNs and plain MTX. Furthermore, cytotoxicity studies were performed on HNGC1 tumor cells. CBSA conjugated SLNs exhibited more potent cytotoxic effect on HNGC1 cells than free MTX. The results clearly indicate prospective of CBSA conjugated SLNs loaded with MTX in brain cancer chemotherapy with augmented ability to bypass blood brain barrier.

Keywords: Cationic bovine serum albumin, solid lipid nanoparticles, methotrexate, brain, tumor targeting, Cationized Albumin Conjugated, Methotrexate (MTX), zeta-potential analysis, Transendothelial transport, brain capillary endothelial cells (BCs), Human neuroglial culture, blood brain barrier, CNS, biocompatible, biodegradable, adsorption, transcytosis, tristearin, soya-lecithin, ethylenediamine, Polydispersity Index Determination, laser doppler anemometry-based multiple angle particle electrophoresis analyzer, astrocytes, Uncoated Solid Lipid Nanoparticles, melt-dispersion method, endocytosis, doxorubicin lo, dextran conjugated dendrim-ers