Potential of solid lipid nanoparticles in brain targeting

Brain is a delicate organ, isolated from general circulation and characterized by the presence of relatively impermeable endothelial cells with tight junctions, enzymatic activity and the presence of active efflux transporter mechanisms (like P-gp efflux). These formidable obstacles often impede drug delivery to the brain. As a result several promising molecules (showing a good potential in in vitro evaluation) are lost from the market for a mere consequence of lack of in vivo response probably because the molecule cannot reach the brain in a sufficient concentration. The options to tailor make molecules for brain, though open to the medical chemist, are a costly proposition in terms of money, manpower and time (almost 50 years). The premedial existing approaches for brain delivery like superficial and ventricular application of chemical or the application of chemicals to brain parenchyma are invasive and hence are less patient friendly, more laborious and require skill and could also damage the brain permanently. In view of these considerations novel drug delivery systems such as the nanoparticles are presently being explored for their suitability for targeted brain delivery. Nanoparticles are solid colloidal particles ranging in size from 1 to 1000 nm (< 1 mu m) and composed of macromolecular material. Nanoparticles could be polymeric or lipidic (SLNs). SLNs are taken up readily by the brain because of their lipidic nature. The bioacceptable and biodegradable nature of SLNs makes them less toxic as compared to polymeric nanoparticles. Supplemented with small size which prolongs the circulation time in blood, feasible scale up for large scale production and absence of burst effect makes them interesting candidates for study. In the present review we will discuss about the barriers to CNS drug delivery, strategies to bypass the blood-brain barrier and characterization methods of SLNs and their usefulness. The proposed mechanism of uptake, methods of prolonging the plasma retention and the in vivo and in vitro methods for assessment will also be discussed in some details. (c) 2008 Elsevier B.V. All rights reserved.