Future prospects of nanoparticles on brain targeted drug delivery

Abstract

To the editor Human brain is restricted and separated from circulatory network by a highly efficient blood brain barrier. This is constituted by relatively impermeable endothelial cells with tight junctions, enzymatic activity and active efflux transport systems. Physiologically, blood-brain barrier is designed in such a manner that it can only permit the transport of molecules essential for functional activity of brain. It efficiently prevents flow of water-soluble molecules from blood circulation into central nervous system, and can also decrease concentration of lipid-soluble molecules by the action of enzymes or efflux pumps [1]. Presently, drug delivery to central nervous system is a major menace as multiple cerebral diseases like Alzheimer’s, brain tumors, prion diseases are cropping up. The blood brain barrier (BBB) represents an insurmountable obstacle for a large number of drugs including antibiotics, antineoplastic agents and a variety of central nervous system (CNS)-active drugs like neuropeptides [1, 2]. This creates a considerable threat for the therapy of cerebral diseases. Currently, nanoparticles are utilized as a drug delivery vehicle. The use of nanoparticles to deliver drugs to the brain by infiltrating blood brain barrier (BBB) may provide a significant strategy to break this impasse. The primary advantage of nanoparticle carrier technology is that it can cross blood brain barrier entrapping the original characteristics of the therapeutic drug molecule. Furthermore, this system may reduce drug leaching in the brain and decrease peripheral toxicity [3]. Drugs that have successfully been transported into the brain using nanoparticle carrier include the hexapeptide dalargin, the dipeptide kytorphin, loperamide, tubocurarine, the NMDA receptor antagonist MRZ 2/ 576, doxorubicin, etc. The nanoparticles may be special vehicle for the treatment of the brain tumors [2] especially for primary and metastatic brain tumors [4]. Currently, nanoparticle iron chelators have been used to treat Alzheimer disease and other neurologic disorders associated with trace metal imbalance [5]. It has been reported that PEGylated polymeric nanoparticles are efficient drug carrier for the delivery of active therapeutic molecules in prion diseases [6]. Strategies for nanoparticle targeting to the brain rely on the presence of its interaction with specific receptor-mediated transport systems in the BBB. For example, polysorbate 80/LDL, transferrin receptor binding antibody (such as OX26), lactoferrin, cellpenetrating peptides and melanotransferrin have been shown its efficacy of delivering a self non-transportable drug into the brain via chimeric construct that can undergo receptor-mediated transcytosis [7–11]. It has been reported that poly (butylcyanoacrylate) nanoparticles is able to deliver hexapeptide dalargin, doxorubicin and other agents into the brain which C. Chakraborty Department of Biotechnology, College of Engineering and Technology, IILM Academy of Higher Learning, Knowledge Park-II, Greater Noida, India