Accessing targeted nanoparticles to the brain: the vascular route.

The blood-brain barrier (BBB), formed by brain capillary endothelial cells, prevents the entry of several drug molecules to the brain, especially molecules hydrophilic in nature. Advanced drug carriers like nanoparticles share the potential to allow entry of therapeutic proteins and genetic molecules into the central nervous system (CNS). Taking a targeting approach by conjugating molecules acting as ligands or monoclonal antibodies with affinity for proteins expressed on the luminal side of brain capillary endothelial cells, the nanoparticles can be designed to enable transport into the brain endothelium, or perhaps even through the endothelium leading to blood to brain transport. Currently, the iron-binding protein transferrin or antibodies raised against the transferrin receptor denote the most feasible molecule for targeting purposes at the BBB. This manuscript reviews the targetability of nanoparticles to the brain capillary endothelial cells, how nanocarriers may enter and transfer through the brain endothelium, and how likely restraints denoted by the threedimensional mesh of the extracellular proteins forming the brain capillary basement membrane challenge the possibilities for enabling transport of large molecules through the BBB encapsulated in nanoparticles.

Uptake and transport of superparamagnetic iron oxide nanoparticles through human brain capillary endothelial cells.

The blood-brain barrier (BBB) formed by brain capillary endothelial cells (BCECs) constitutes a firm physical, chemical, and immunological barrier, making the brain accessible to only a few percent of potential drugs intended for treatment inside the central nervous system. With the purpose of overcoming the restraints of the BBB by allowing the transport of drugs, siRNA, or DNA into the brain, a novel approach is to use superparamagnetic iron oxide nanoparticles (SPIONs) as drug carriers. The aim of this study was to investigate the ability of fluorescent SPIONs to pass through human brain microvascular endothelial cells facilitated by an external magnet. The ability of SPIONs to penetrate the barrier was shown to be significantly stronger in the presence of an external magnetic force in an in vitro BBB model. Hence, particles added to the luminal side of the in vitro BBB model were found in astrocytes cocultured at a remote distance on the abluminal side, indicating that particles were transported through the barrier and taken up by astrocytes. Addition of the SPIONs to the culture medium did not negatively affect the viability of the endothelial cells. The magnetic force-mediated dragging of SPIONs through BCECs may denote a novel mechanism for the delivery of drugs to the brain.

Nanoparticle-derived non-viral genetic transfection at the blood-brain barrier to enable neuronal growth factor delivery by secretion from brain endothelium.

Brain capillary endothelial cells form the blood-brain barrier (BBB) that denotes a major restraint for drug entry to the brain. The identification of many new targets to treat diseases in the brain demands novel thinking in drug design as new therapeutics could often be proteins and molecules of genetic origins like siRNA, miRNA and cDNA. Such molecules are otherwise prevented from entry into the brain unless encapsulated in drug carriers. The desirable entry of such large, hydrophilic molecules should be made by formulation of particular drug carriers that will enable their transport into the brain endothelium, or even through the endothelium and into the brain. This manuscript reviews the potential of different drug-carriers for therapy to the brain with respect to their targetability, biocompatibility, toxicity and biodegradability.

Towards hot electron mediated charge exchange in hyperthermal energy ion-surface interactions.

We have made Na (+) and He (+) ions incident on the surface of solid state tunnel junctions and measured the energy loss due to atomic displacement and electronic excitations. Each tunnel junction consists of an ultrathin film metal-oxide-semiconductor device which can be biased to create a band of hot electrons useful for driving chemical reactions at surfaces. Using the binary collision approximation and a nonadiabatic model that takes into account the time-varying nature of the ion-surface interaction, the energy loss of the ions is reproduced. The energy loss for Na (+) ions incident on the devices shows that the primary energy loss mechanism is the atomic displacement of Au atoms in the thin film of the metal-oxide-semiconductor device. We propose that neutral particle detection of the scattered flux from a biased device could be a route to hot electron mediated charge exchange.

Adenolipoma of the thyroid gland.

A case of rare fat-cell-containing adenoma, an adenolipoma, in the thyroid gland is reported. Previously documented cases are reviewed. Diffuse lipomatosis of the thyroid, amyloid goitre with adipose tissue, and the relationship between lipomatosis and adenolipoma are discussed.