Treatment for brain cancer usually includes surgery, radiation therapy, and systemic chemotherapy. Nonetheless, the median survival rate for patients with primary brain tumors after surgery and radiation therapy is nine months, with approximately 10% living two years (Orive, Ali, Anitua, Pedraz, & Emerich, 2010). . Ultimately, brain tumors are responsible for approximately 13,000 deaths each year in the United States (Greenlee, Murray, Bolden, & Wingo, 2000). Limited drug uptake by tumor cells, intracellular drug metabolism, and cellular resistance mechanisms have all blocked the progression of brain cancer therapies (Orive, Ali, Anitua, Pedraz, & Emerich, 2010). However, the main obstacle remains the existence of the blood-brain barrier (BBB), a structure formed by the tight junctions between endothelial cells and astrocytes which strongly limits the levels of pinocytosis, thus restricting the passage of compounds from the blood to the extracellular environment. environment of the brain. Generally, most endothelial barriers allow the passive transport of nanoparticles less than 150 nm in diameter, but the BBB only allows the diffusion of small, lipid-soluble molecules (<500 Da MW), neutrally charged (Pardridge, 2002). As a result, the passage of materials into the brain parenchyma is largely inhibited for many diagnostic and therapeutic molecules synthesized for the treatment of CNS disorders (Farokhzad & Langer, 2006). While the substances that can cross the BBB depend on the aqueous paracellular pathway, the transcellular lipophilic pathway, transport proteins, receptor-mediated transcytosis, or adsorption-mediated transcytosis, the latter two are the major pathways of delivery of nanoparticles (NPs) across the BBB. Adsorbent-mediated transcytic...... middle of paper ...... eaten once into the bloodstream, which again induces rapid elimination from the body. Due to the numerous sensing pathways of RES, extending circulation time is essential for developing effective drug treatment for the brain. Accordingly, nanoparticles have been functionalized with various surface molecules to block RES recognition, prolong circulation time, and prevent agglomeration, including dextran and polyvinyl alcohol (PVA) (Moore, Marecos , Bogdanov and Weissleder, 2000; However, the most commonly practiced fixation is covalent fixation of polyethylene glycol (PEG) as a means of extending circulation time. PEGylation is considered to suppress macrophage recognition via reduced protein adsorption and surface opsonization, likely due to the creation of a steric barrier on the nanoparticle surface (Orive, Ali, Anitua, Pedraz, and Emerich, 2010).