Cationic ligand appended nanoconstructs: A prospective strategy for brain targeting

The objective of present research was to evaluate the potential of engineered solid lipid nanoparticles (SLNs) as vectors to bypass the blood brain barrier. Anti-cancer agent, doxorubicin (DOX) loaded SLNs were prepared and conjugated with cationic bovine serum albumin (CBSA). The formation of CBSA tethered and plain SLNs were characterized by FTIR, NMR, and TEM analyses. Physicochemical parameters such as particle size/polydispersity index and zeta-potential were also determined. Cellular uptake studies on HNGC-1 cell lines depicted almost six times enhanced uptake of ligand conjugated SLNs as compared to plain DOX solution. Furthermore, CBSA conjugated formulation was more cytotoxic as compared to free drug or unconjugated SLNs. Transendothelial studies showed maximum transcytosis ability of CBSA conjugated SLNs across brain capillary endothelial cells. In vivo pharmacokinetic parameters and biodistribution pattern demonstrated efficiency of the system for spatial and temporal delivery of DOX to brain tissues. Lastly, hematological, nephrotoxic as well as hepatotoxic data suggested CBSA conjugated formulations to be less immunogenic compared to plain formulations. (C) 2011 Elsevier B.V. All rights reserved.