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Drug Delivery Through Blood Brain Barrier:Taming the Bottleneck in CNS Therapeutics
Although many agents have therapeutic potentials for Central Nervous System (CNS) diseases, few of these agents have been clinically used because of the brain barriers. Physiological barriers like the blood-brain barrier and blood-cerebrospinal fluid barrier as well as various efflux transporter proteins make the entry of drugs into the central nervous system very difficult. Different strategies for efficient CNS delivery have been studied. This review presents the current approaches to facilitate penetration across these barriers for enhanced drug delivery to the CNS.
Blood Brain Barrier, CNS Drug Delivery.
- Schlosshauer B. The blood-brain barrier: morphology, molecules, and neurothelin. Bioassays. 1993; 15:341–6. https:// doi.org/10.1002/bies.950150508 PMid:8102053
- Brightman MW, Zis K, Anders J. Morphology of cerebral endothelium and astrocytes as determinants of the neuronal microenvironment. In: Hossmann KA, Klatzo I, editors. Cerebrovascular transport mechanisms. Acta Neuropathologica Supplementum. Berlin: Springer; 1983. p. 21–33. https://doi.org/10.1007/978-3-642-68970-3_2 PMid:6346778
- Martin B, Robert L, Henry B, Mathiowitz E. Encyclopedia of controlled drug delivery, Vol. l, New York: John Wiley and Sons Inc; l999. p. 184-210.
- Pankajavalli R. The role of P-glycoprotein in the bloodbrain barrier. Einstein Quart J Biol Med. 2003; 19:160–5.
- Dwibhashyam VS, Nagappa AN. Strategies for enhanced drug delivery to the central nervous system. IJPS. 2008; 70(2):145–53. https://doi.org/10.4103/0250-474X.41446 PMid:20046703 PMCid:PMC2792490
- Lu C-T, Zhao Y-Z, Wong HL, Cai J, Peng L, Tian X-Q. Current approaches to enhance CNS delivery of drugs across the brain barriers. Int. J Nanomedicine. 2014; 9:2241– 57. https://doi.org/10.2147/IJN.S61288 PMid:24872687 PMCid:PMC4026551
- Bodor N. A strategy for delivering peptides into the central nervous system by sequential metabolism. Science. l992; 257:1698–700.
- Smith QR. Carrier-mediated transport to enhance drug delivery to brain. International Congress Series. 2005; 1277:63–74. https://doi.org/10.1016/j.ics.2005.02.012
- Kang YS, Bickel U, Pardridge WM. Pharmacokinetics and saturable blood-brain barrier transport of biotin bound to a conjugate of avidin and a monoclonal antibody to the transferrin receptor. Drug Metab Dispos. 1994; 22(1):99– 105.PMid:8149897
- Wong HL, Wu XY, Bendayan R. Nanotechnological advances for the delivery of CNS therapeutics. Adv Drug Deliv Rev. 2012; 64:686–700. https://doi.org/10.1016/j.addr.2011.10.007 PMid:22100125
- Kreuter J. Nanoparticulate systems for brain delivery of drugs. Adv Drug Deliv Rev. 2001; 47:65–81. https://doi.org/10.1016/S0169-409X(00)00122-8
- Scheld WM. Drug delivery to the central nervous system: general principles and relevance to therapy for infections of the central nervous system. Rev Infect Dis. 1989; 11 Suppl 7:S1669–90. https://doi.org/10.1093/clinids/11.Supplement_7.S1669 PMid:2690302
- Rapoport SI, Robinson PJ. Tight-junctional modification as the basis of osmotic opening of the blood–brain barrier. Ann N Y Acad Sci. 1986; 481:250–67. https://doi.org/10.1111/j.1749-6632.1986.tb27155.x
- Cloughesy TF, Black KL. Pharmacological blood–brain barrier modification for selective drug delivery. J Neurooncol. 1995; 26:125–32. https://doi.org/10.1007/BF01060218
- Cho CW, Lin Y, Cobb WN. Ultrasound-induced mild hyperthermia as a novel approach to increase drug uptake in brain micro vessel endothelial cells. Pharm Res. 2002; 115:413–24.
- Mathison S, Nagilla R, Kompella UB. Nasal route for direct delivery of solutes to the central nervous system: fact or fiction? J Drug Target. 1998; 5:415–41. https://doi.org/10.3109/10611869808997870 PMid:9783675
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