Crossing the Blood-Brain Barrier: A Review on Drug Delivery Strategies for Treatment of the Central Nervous System Diseases

Author(s): Nur Izzati Mansor, Norshariza Nordin*, Farahidah Mohamed, King Hwa Ling, Rozita Rosli, Zurina Hassan

Journal Name: Current Drug Delivery

Volume 16 , Issue 8 , 2019

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Graphical Abstract:


Many drugs have been designed to treat diseases of the central nervous system (CNS), especially neurodegenerative diseases. However, the presence of tight junctions at the blood-brain barrier has often compromised the efficiency of drug delivery to target sites in the brain. The principles of drug delivery systems across the blood-brain barrier are dependent on substrate-specific (i.e. protein transport and transcytosis) and non-specific (i.e. transcellular and paracellular) transport pathways, which are crucial factors in attempts to design efficient drug delivery strategies. This review describes how the blood-brain barrier presents the main challenge in delivering drugs to treat brain diseases and discusses the advantages and disadvantages of ongoing neurotherapeutic delivery strategies in overcoming this limitation. In addition, we discuss the application of colloidal carrier systems, particularly nanoparticles, as potential tools for therapy for the CNS diseases.

Keywords: Blood-brain barrier, central nervous system, neurodegenerative diseases, drug delivery system, nanoparticles, colloidal carrier system.

Klink, D.; Schindelhauer, D.; Laner, A.; Tucker, T.; Bebok, Z.; Schwiebert, E.M.; Boyd, A.C.; Scholte, B.J. Gene delivery systems--gene therapy vectors for cystic fibrosis. J. Cyst. Fibros., 2004, 3(Suppl. 2), 203-212.
[] [PMID: 15463959]
Misra, A.; Ganesh, S.; Shahiwala, A.; Shah, S.P. Drug delivery to the central nervous system: A review. J. Pharm. Pharm. Sci., 2003, 6(2), 252-273.
[PMID: 12935438]
Begley, D.J. Delivery of therapeutic agents to the central nervous system: The problems and the possibilities. Pharmacol. Ther., 2004, 104, 29-45.
Hakkarainen, J.J. In vitro Cell models in predicting blood-brain barrier permeability of drugs. Unpublished doctoral dissertation, University of Eastern, Finland, 2013.
Liddelow, S.A. Fluids and barriers of the CNS: A historical viewpoint. Fluids Barriers CNS, 2011, 8(1), 2.
[] [PMID: 21349150]
Hawkins, B.T.; Davis, T.P. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol. Rev., 2005, 57(2), 173-185.
[] [PMID: 15914466]
Pardridge, W.M. Blood-brain barrier delivery of protein and non-viral gene therapeutics with molecular Trojan horses. J. Control. Release, 2007, 122(3), 345-348.
[] [PMID: 17512078]
Rodríguez-Baeza, A.; Reina-de la Torre, F.; Poca, A.; Martí, M.; Garnacho, A. Morphological features in human cortical brain microvessels after head injury: A three-dimensional and immunocytochemical study. Anat. Rec. A Discov. Mol. Cell. Evol. Biol., 2003, 273(1), 583-593.
[] [PMID: 12808643]
Begley, D.J. Structure and function of the blood-brain barrier. Enhancement in Drug Delivery; CRC Press: Boca Raton, Finland, 2007.
Rubin, L.L.; Staddon, J.M. The cell biology of the blood-brain barrier. Annu. Rev. Neurosci., 1999, 22, 11-28.
[] [PMID: 10202530]
Dejana, E.; Lampugnani, M.G.; Martinez-Estrada, O.; Bazzoni, G. The molecular organization of endothelial junctions and their functional role in vascular morphogenesis and permeability. Int. J. Dev. Biol., 2000, 44(6), 743-748.
[PMID: 11061439]
Tajes, M.; Ramos-Fernández, E.; Weng-Jiang, X.; Bosch-Morató, M.; Guivernau, B.; Eraso-Pichot, A.; Salvador, B.; Fernàndez-Busquets, X.; Roquer, J.; Muñoz, F.J. The blood-brain barrier: Structure, function and therapeutic approaches to cross it. Mol. Membr. Biol., 2014, 31(5), 152-167.
[] [PMID: 25046533]
González-Mariscal, L.; Betanzos, A.; Nava, P.; Jaramillo, B.E. Tight junction proteins. Prog. Biophys. Mol. Biol., 2003, 81(1), 1-44.
[] [PMID: 12475568]
Zihni, C.; Mills, C.; Matter, K.; Balda, M.S. Tight junctions: From simple barriers to multifunctional molecular gates. Nat. Rev. Mol. Cell Biol., 2016, 17(9), 564-580.
[] [PMID: 27353478]
Brown, D.; Stow, J.L. Protein trafficking and polarity in kidney epithelium: From cell biology to physiology. Physiol. Rev., 1996, 76(1), 245-297.
[] [PMID: 8592730]
Butt, A.M.; Jones, H.C.; Abbott, N.J. Electrical resistance across the blood-brain barrier in anaesthetized rats: A developmental study. J. Physiol., 1990, 429(1), 47-62.
[] [PMID: 2277354]
Polakis, P.; Taddei, A.; Czupalla, C.J.; Reis, M.; Felici, A.; Wolburg, H. Formation of the blood-brain barrier: Wnt signaling seals the deal. J. Cell Biol., 2008, 183(3), 371-373.
[] [PMID: 18955557]
Derada, T.C.; de Goede, P.; Kamermans, A.; de Vries, H.E. Molecular alterations of the blood-brain barrier under inflammatory conditions: The role of endothelial to mesenchymal transition. Biochim. Biophys. Acta, 2016, 1862(3), 452-460.
[] [PMID: 26493443]
McCarthy, K.M.; Skare, I.B.; Stankewich, M.C.; Furuse, M.; Tsukita, S.; Rogers, R.A.; Lynch, R.D.; Schneeberger, E.E. Occludin is a functional component of the tight junction. J. Cell Sci., 1996, 109(Pt 9), 2287-2298.
[PMID: 8886979]
Furuse, M.; Fujita, K.; Hiiragi, T.; Fujimoto, K.; Tsukita, S. A single gene product, Caludin-1 and -2 novel integral membrane proteins localizing at tight junctions with no sequence similarity to Occludin. J. Cell Biol., 1998, 141, 1539-1550.
[] [PMID: 9647647]
Stamatovic, S.M.; Keep, R.F.; Andjelkovic, A.V. Brain endothelial cell-cell junctions: How to “open” the blood brain barrier. Curr. Neuropharmacol., 2008, 6(3), 179-192.
[] [PMID: 19506719]
Luissint, A.C.; Artus, C.; Glacial, F.; Ganeshamoorthy, K.; Couraud, P.O. Tight junctions at the blood brain barrier: physiological architecture and disease-associated dysregulation. Fluids Barriers CNS, 2012, 9(1), 23.
[] [PMID: 23140302]
Koto, T.; Takubo, K.; Ishida, S.; Shinoda, H.; Inoue, M.; Tsubota, K.; Okada, Y.; Ikeda, E. Hypoxia disrupts the barrier function of neural blood vessels through changes in the expression of claudin-5 in endothelial cells. Am. J. Pathol., 2007, 170(4), 1389-1397.
[] [PMID: 17392177]
Bauer, H.; Traweger, A. Tight junctions of the blood-brain barrier - A molecular gatekeeper. CNS Neurol. Disord. Drug Targets, 2016, 15(9), 1016-1029.
[] [PMID: 27633783]
Wolburg, H.; Wolburg-Buchholz, K.; Kraus, J.; Rascher-Eggstein, G.; Liebner, S.; Hamm, S.; Duffner, F.; Grote, E.H.; Risau, W.; Engelhardt, B. Localization of claudin-3 in tight junctions of the blood-brain barrier is selectively lost during experimental autoimmune encephalomyelitis and human glioblastoma multiforme. Acta Neuropathol., 2003, 105(6), 586-592.
[] [PMID: 12734665]
Furuse, M.; Hirase, T.; Itoh, M.; Nagafuchi, A.; Yonemura, S.; Tsukita, S.; Tsukita, S. Occludin: A novel integral membrane protein localizing at tight junctions. J. Cell Biol., 1993, 123(6 Pt 2), 1777-1788.
[] [PMID: 8276896]
Hirase, T.; Kawashima, S.; Wong, E.Y.M.; Ueyama, T.; Rikitake, Y.; Tsukita, S.; Yokoyama, M.; Staddon, J.M. Regulation of tight junction permeability and occludin phosphorylation by Rhoa-p160ROCK-dependent and -independent mechanisms. J. Biol. Chem., 2001, 276(13), 10423-10431.
[] [PMID: 11139571]
Hirase, T.; Staddon, J.M.; Saitou, M.; Ando-Akatsuka, Y.; Itoh, M.; Furuse, M.; Fujimoto, K.; Tsukita, S.; Rubin, L.L. Occludin as a possible determinant of tight junction permeability in endothelial cells. J. Cell Sci., 1997, 110(Pt 14), 1603-1613.
[PMID: 9247194]
Wong, V.; Gumbiner, B.M. A synthetic peptide corresponding to the extracellular domain of occludin perturbs the tight junction permeability barrier. J. Cell Biol., 1997, 136(2), 399-409.
[] [PMID: 9015310]
Fraemohs, L.; Koenen, R.R.; Ostermann, G.; Heinemann, B.; Weber, C.; Koenen, R.R. The functional interaction of the β 2 integrin lymphocyte function-associated antigen-1 with junctional adhesion molecule-A is mediated by the I domain. J. Immunol., 2004, 173(10), 6259-6264.
[] [PMID: 15528364]
Aurrand-Lions, M.; Lamagna, C.; Dangerfield, J.P.; Wang, S.; Herrera, P.; Nourshargh, S.; Imhof, B.A. Junctional adhesion molecule-C regulates the early influx of leukocytes into tissues during inflammation. J. Immunol., 2005, 174(10), 6406-6415.
[] [PMID: 15879142]
Breier, G.; Breviario, F.; Caveda, L.; Berthier, R.; Schnürch, H.; Gotsch, U.; Vestweber, D.; Risau, W.; Dejana, E. Molecular cloning and expression of murine vascular endothelial-cadherin in early stage development of cardiovascular system. Blood, 1996, 87(2), 630-641.
[PMID: 8555485]
Clevers, H.; Nusse, R. Review Wnt / b -Catenin signaling and Disease. Cell, 2012, 149(June 8), 1192-1205.
Reis, M.; Liebner, S. Wnt signaling in the vasculature. Exp. Cell Res., 2013, 319(9), 1317-1323.
[] [PMID: 23291327]
Clevers, H. Wnt/β-catenin signaling in development and disease. Cell, 2006, 127(3), 469-480.
[] [PMID: 17081971]
MacDonald, B.T.; Tamai, K.; He, X. Wnt/β-catenin signaling: components, mechanisms, and diseases. Dev. Cell, 2009, 17(1), 9-26.
[] [PMID: 19619488]
Paolinelli, R.; Corada, M.; Ferrarini, L.; Devraj, K.; Artus, C.; Czupalla, C.J.; Rudini, N.; Maddaluno, L.; Papa, E.; Engelhardt, B.; Couraud, P.O.; Liebner, S.; Dejana, E. Wnt activation of immortalized brain endothelial cells as a tool for generating a standardized model of the blood brain barrier in vitro. PLoS One, 2013, 8(8)e70233
[] [PMID: 23940549]
Liebner, S.; Gerhardt, H.; Wolburg, H. Differential expression of endothelial beta-catenin and plakoglobin during development and maturation of the blood-brain and blood-retina barrier in the chicken. Dev. Dyn., 2000, 217(1), 86-98.
[] [PMID: 10679932]
Liebner, S.; Corada, M.; Bangsow, T.; Babbage, J.; Taddei, A.; Czupalla, C.J.; Reis, M.; Felici, A.; Wolburg, H.; Fruttiger, M.; Taketo, M.M.; von Melchner, H.; Plate, K.H.; Gerhardt, H.; Dejana, E. Wnt/β-catenin signaling controls development of the blood-brain barrier. J. Cell Biol., 2008, 183(3), 409-417.
[] [PMID: 18955553]
Daneman, R.; Agalliu, D.; Zhou, L.; Kuhnert, F.; Kuo, C.J.; Barres, B.A. Wnt/beta-catenin signaling is required for CNS, but not non-CNS, angiogenesis. Proc. Natl. Acad. Sci. USA, 2009, 106(2), 641-646.
[] [PMID: 19129494]
Tran, K.A.; Zhang, X.; Predescu, D. Endothelial β-catenin signaling is required for maintaining adult blood-brain barrier integrity and CNS homeostasis. Circulation, 2016, 133(2), 177-186.
[] [PMID: 26538583]
Ciani, L.; Salinas, P.C. WNTs in the vertebrate nervous system: From patterning to neuronal connectivity. Nat. Rev. Neurosci., 2005, 6(5), 351-362.
[] [PMID: 15832199]
Artus, C.; Glacial, F.; Ganeshamoorthy, K.; Ziegler, N.; Godet, M.; Guilbert, T.; Liebner, S.; Couraud, P.O. The Wnt/planar cell polarity signaling pathway contributes to the integrity of tight junctions in brain endothelial cells. J. Cereb. Blood Flow Metab., 2014, 34(3), 433-440.
[] [PMID: 24346691]
Ranade, V.V.; Holinger, M.A. Drug Delivery, 2nd ed; CRC Press: Boca Raton, FL, 2004.
Troy, D.B.; Beringer, P. Remington: The Science and Practice of Pharmacy Lippincott, William and Wilkins: Baltimore; , 2006.
Jain, K.K. Drug Delivery Systems - An Overview; Humana Press: USA, 2008.
van Hoogdalem, E.; de Boer, A.G.; Breimer, D.D. Pharmacokinetics of rectal drug administration, Part I. General considerations and clinical applications of centrally acting drugs. Clin. Pharmacokinet., 1991, 21(1), 11-26.
[] [PMID: 1717195]
Alexander, K. Dosage Forms and Their Routes of Administration.In: Pharmacology: Principle and practice; Hacker, M.; Messe, W.S.; Bachmann, K.A., Eds.; Elsevier Inc.: USA, 2009, pp. 1-608.
Baviskar, P.; Bedse, A.; Sadique, S.; Kunde, V.; Jaiswal, S. Drug delivery on rectal absorption: Suppositories. Int. J. Pharm. Sci. Rev. Res., 2013, 21(1), 70-76.
De Boer, A.G.; De Leede, L.G.; Breimer, D.D. Drug absorption by sublingual and rectal routes. Br. J. Anaesth., 1984, 56(1), 69-82.
[] [PMID: 6140933]
Graves, N.M.; Kriel, R.L. Rectal administration of antiepileptic drugs in children. Pediatr. Neurol., 1987, 3(6), 321-326.
[] [PMID: 3334021]
Choonara, I.A. Giving drugs per rectum for systemic effect. Arch. Dis. Child., 1987, 62(8), 771-772.
[] [PMID: 3662579]
Gulati, N.; Gupta, H. Parenteral drug delivery: A review. Recent Pat. Drug Deliv. Formul., 2011, 5(2), 133-145.
[] [PMID: 21453250]
Florence, A.T.; Salole, E.G. Routes of Drug Administration, 1st ed; Butterworth-Heinemann: London, 1990.
Pergolizzi, J.V.; Raffa, R.; Taylor, R. Prophylaxis of postoperative nausea and vomiting in adolescent patients: A review with emphasis on combination of fixed-dose ondansetron and transdermal scopolamine. J. Drug Deliv., 2011.2011426813
[] [PMID: 21773046]
Pergolizzi, J.V., Jr; Philip, B.K.; Leslie, J.B.; Taylor, R., Jr; Raffa, R.B. Perspectives on transdermal scopolamine for the treatment of postoperative nausea and vomiting. J. Clin. Anesth., 2012, 24(4), 334-345.
[] [PMID: 22608591]
McKeran, R.O.; Firth, G.; Oliver, S.; Uttley, D.; O’Laoire, S. A potential application for the intracerebral injection of drugs entrapped within liposomes in the treatment of human cerebral gliomas. J. Neurol. Neurosurg. Psychiatry, 1985, 48(12), 1213-1219.
[] [PMID: 2418156]
Ding, H. Modified-release drug products and drug devices. In: Applied pharmaceutical and pharmacokinetics, 7th ed; Shargel, L.; Yu, A.B.C., Eds.; Appleton & Lange McGraw-Hill Education: New York, 2016, pp. 567-613.
Wang, B.; Siahaan, T.J.; Soltero, R. Drug Delivery: Principles and Applications; John Wiley & Sons, Inc.: New Jersey, NJ, 2005.
Pottiez, G.; Flahaut, C.; Cecchelli, R.; Karamanos, Y. Understanding the blood-brain barrier using gene and protein expression profiling technologies. Brain Res. Brain Res. Rev., 2009, 62(1), 83-98.
[] [PMID: 19770003]
Tortora, G.J.; Derrickson, B.D. Principles of anatomy and physiology, 12th ed; John Wiley: Sons, USA, 2009.
Neuwelt, E.A.; Goldman, D.L.; Dahlborg, S.A.; Crossen, J.; Ramsey, F.; Roman-Goldstein, S.; Braziel, R.; Dana, B. Primary CNS lymphoma treated with osmotic blood-brain barrier disruption: Prolonged survival and preservation of cognitive function. J. Clin. Oncol., 1991, 9(9), 1580-1590.
[] [PMID: 1875220]
Abbott, N.J.; Patabendige, A.A.; Dolman, D.E.; Yusof, S.R.; Begley, D.J. Structure and function of the blood-brain barrier. Neurobiol. Dis., 2010, 37, 13-25.
Abbott, N.J.; Rönnbäck, L.; Hansson, E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat. Rev. Neurosci., 2006, 7(1), 41-53.
Miller, G. Drug targeting. Breaking down barriers. Science, 2002, 297, 1116-1118.
Betz, A.L.; Bowman, P.D.; Goldstein, G.W. Hexose transport in microvascular endothelial cells cultured from bovine retina. Exp. Eye Res., 1983, 36(2), 269-277.
[] [PMID: 6337860]
Ueno, M. Mechanisms of the penetration of blood-borne substances into the brain. Curr. Neuropharmacol., 2009, 7(2), 142-149.
[] [PMID: 19949573]
Duffy, K.R.; Pardridge, W.M. Blood-brain barrier transcytosis of insulin in developing rabbits. Brain Res., 1987, 420(1), 32-38.
[] [PMID: 3315116]
Holly, J.; Perks, C. The role of insulin-like growth factor binding proteins. Neuroendocrinology, 2006, 83(3-4), 154-160.
[] [PMID: 17047378]
Terasaki, T.; Ohtsuki, S. Brain-to-blood transporters for endogenous substrates and xenobiotics at the blood-brain barrier: An overview of biology and methodology. NeuroRx, 2005, 2(1), 63-72.
[] [PMID: 15717058]
Terasaki, T.; Hosoya, K. The blood-brain barrier efflux transporters as a detoxifying system for the brain. Adv. Drug Deliv. Rev., 1999, 36(2-3), 195-209.
[] [PMID: 10837716]
Genka, S.; Deutsch, J.; Shetty, U.H.; Stahle, P.L.; John, V.; Lieberburg, I.M.; Ali-Osman, F.; Rapoport, S.I.; Greig, N.H. Development of lipophilic anticancer agents for the treatment of brain tumors by the esterification of water-soluble chlorambucil. Clin. Exp. Metastasis, 1993, 11(2), 131-140.
[] [PMID: 8444006]
Bodor, N.; Kamiski, J.J. Prodrugs and site-specific chemical delivery systems. Annu. Rep. Med. Chem., 1987, 22, 303-313.
Rautioa, J.; Chikhale, P.J. Drug delivery systems for brain tumor therapy. Curr. Pharm. Des., 2004, 10(12), 1341-1353.
[] [PMID: 15134485]
Karpagavalli, L.; Vigneshwar, M.; Monisha, M.; Prabavathi, M.; Prasanth, P.; Zairudeen, K. A review on prodrugs. Int. J. Novel Trends Pharm. Sci., 2016, 6(1), 1-5.
Lawther, B.K.; Kumar, S.; Krovvidi, H. Blood - brain barrier. Contin. Educ. Anaesth. Crit. Care Pain, 2017, 11(4), 128-132.
Rapoport, S.I. Osmotic opening of the blood-brain barrier: Principles, mechanism, and therapeutic applications. Cell. Mol. Neurobiol., 2000, 20(2), 217-230.
[] [PMID: 10696511]
Chio, C.C.; Baba, T.; Black, K.L. Selective blood-tumor barrier disruption by leukotrienes. J. Neurosurg., 1992, 77(3), 407-410.
[] [PMID: 1506887]
Black, K.L.; Baba, T.; Pardridge, W.M. Enzymatic barrier protects brain capillaries from leukotriene C4. J. Neurosurg., 1994, 81(5), 745-751.
[] [PMID: 7931622]
Kroll, R.A.; Neuwelt, E.A. Outwitting the blood-brain barrier for therapeutic purposes: Osmotic opening and other means. Neurosurgery, 1998, 42(5), 1083-1099.
[] [PMID: 9588554]
Chandran, S.; Prasanna, P.M. Blood brain barrier and various strategies for drug delivery to brain. BBB, 2014, 2(3), 504-520.
Salahuddin, T.S.; Johansson, B.B.; Kalimo, H.; Olsson, Y. Structural changes in the rat brain after carotid infusions of hyperosmolar solutions: A light microscopic and immunohistochemical study. Neuropathol. Appl. Neurobiol., 1988, 14(6), 467-482.
[] [PMID: 3147406]
Hersh, D.S.; Wadajkar, A.S.; Roberts, N.; Perez, J.G.; Connolly, N.P.; Frenkel, V.; Winkles, J.A.; Woodworth, G.F.; Kim, A.J. Evolving drug delivery strategies to overcome blood brain barrier. Curr. Pharm. Des., 2016, 22(9), 1177-1193.
[] [PMID: 26685681]
Sanovich, E.; Bartus, R.T.; Friden, P.M.; Dean, R.L.; Le, H.Q.; Brightman, M.W. Pathway across blood-brain barrier opened by the bradykinin agonist, RMP-7. Brain Res., 1995, 705(1-2), 125-135.
[] [PMID: 8821743]
Bartus, R.T.; Elliott, P.J.; Dean, R.L.; Hayward, N.J.; Nagle, T.L.; Huff, M.R.; Snodgrass, P.A.; Blunt, D.G. Controlled modulation of BBB permeability using the bradykinin agonist, RMP-7. Exp. Neurol., 1996, 142(1), 14-28.
[] [PMID: 8912895]
Fike, J.R.; Gobbel, G.T.; Mesiwala, A.H.; Shin, H.J.; Nakagawa, M.; Lamborn, K.R.; Seilhan, T.M.; Elliott, P.J. Cerebrovascular effects of the bradykinin analog RMP-7 in normal and irradiated dog brain. J. Neurooncol., 1998, 37(3), 199-215.
[] [PMID: 9524078]
Bidanset, D.J.; Placidi, L.; Rybak, R.; Palmer, J.; Sommadossi, J.P.; Kern, E.R. Intravenous infusion of cereport increases uptake and efficacy of acyclovir in herpes simplex virus-infected rat brains. Antimicrob. Agents Chemother., 2001, 45(8), 2316-2323.
[] [PMID: 11451691]
Liu, D.; Yang, F.; Xiong, F.; Gu, N. The smart drug delivery system and its clinical potential. Theranostics, 2016, 6(9), 1306-1323.
[] [PMID: 27375781]
Torchilin, V.P. Recent advances with liposomes as pharmaceutical carriers. Nat. Rev. Drug Discov., 2005, 4(2), 145-160.
[] [PMID: 15688077]
Tiwari, G.; Tiwari, R.; Sriwastawa, B.; Bhati, L.; Pandey, S.; Pandey, P.; Bannerjee, S.K. Drug delivery systems: An updated review. Int. J. Pharm. Investig., 2012, 2(1), 2-11.
[] [PMID: 23071954]
Jain, N.K.; Rana, A.C.; Jain, S.K. Brain drug delivery system bearing dopamine hydrochloride for effective management of parkinsonism. Drug Dev. Ind. Pharm., 1998, 24(7), 671-675.
[] [PMID: 9876513]
Mohanraj, V.J.; Chen, Y. Nanoparticles- A review. Trop. J. Pharm. Res., 2006, 5(1), 561-573.
Tiyaboonchai, W. Chitosan nanoparticles: A promising system for drug delivery. NUJST, 2003, 11(3), 51-66.
Chia, N.P.H. Nanomedicine and Cancer. Rep. Nanotech. Society; University of Wisconsin: Madison, 2005.
Lai, W.F.; Lin, M.C.M. Nucleic acid delivery with chitosan and its derivatives. J. Control. Release, 2009, 134(3), 158-168.
[] [PMID: 19100795]
Sundar, S.; Kundu, J.; Kundu, S.C. Biopolymeric nanoparticles. Sci. Technol. Adv. Mater., 2010, 11(1)014104
[] [PMID: 27877319]
Hans, M.L. Synthesis, characterization, and application of biodegradable polymeric prodrug micelles for long-term drug delivery PhD thesis, Drexel University, Pennsylvania, 2005.
Khademhosseini, A.; Langer, R. Nanobiotechnolgy for tissue engineering and drug delivery. Chem. Eng. Prog., 2006, 102, 38-42.
Gaur, U.; Sahoo, S.K.; De, T.K.; Ghosh, P.C.; Maitra, A.; Ghosh, P.K. Biodistribution of fluoresceinated dextran using novel nanoparticles evading reticuloendothelial system. Int. J. Pharm., 2000, 202(1-2), 1-10.
Nafee, N.; Taetz, S.; Schneider, M.; Schaefer, U.F.; Lehr, C. Chitosan-coated PLGA nanoparticles for DNA/RNA delivery: Effect of the formulation parameters on complexation and transfection of antisense oligonucleotides. Nanomedicine: NBM, 2007, 3(3), 173-183.
Kim, I.Y.; Seo, S.J.; Moon, H.S.; Yoo, M.K.; Park, I.Y.; Kim, B.C.; Cho, C.S. Chitosan and its derivatives for tissue engineering applications. Biotechnol. Adv., 2008, 26(1), 1-21.
[] [PMID: 17884325]
Zhang, Y.; Yang, M.; Portney, N.G. Zeta potential: A surface electrical characteristic to probe the interaction of nanoparticles with normal and cancer human breast epithelial cells. Biomed. Microdevices, 2008, 10, 321-328.
RaviKumar. M.N.V.; Bakowsky, U.; Lehr, C.M. Preparation and characterization of cationic PLGA nanospheres as DNA carriers. Biomaterials, 2004, 25, 1771-1777.
Honary, S.; Zahir, F. Effect of zeta potential on the properties of nano-drug delivery system - A review (Part 2). Trop. J. Pharm. Res., 2012, 12(2), 265-273.
Bala, I.; Hariharan, S.; Kumar, M.N.V.R. PLGA nanoparticles in drug delivery: The state of the art. Crit. Rev. Ther. Drug Carrier Syst., 2004, 21(5), 387-422.
[] [PMID: 15719481]
Suri, S.S.; Fenniri, H.; Singh, B. Nanotechnology-based drug delivery systems. J. Occup. Med. Toxicol., 2007, 2, 16.
[] [PMID: 18053152]
Wilczewska, A.Z.; Niemirowicz, K.; Markiewicz, K.H.; Car, H. Nanoparticles as drug delivery systems. Pharmacol. Rep., 2012, 64(5), 1020-1037.
[] [PMID: 23238461]
De Jong, W.H.; Borm, P.J. Drug delivery and nanoparticles:applications and hazards. Int. J. Nanomed., 2008, 3(2), 133-149.
[] [PMID: 18686775]
Bazile, D.; Prud’homme, C.; Bassoullet, M.T.; Marlard, M.; Spenlehauer, G.; Veillard, M. Stealth Me.PEG-PLA nanoparticles avoid uptake by the mononuclear phagocytes system. J. Pharm. Sci., 1995, 84(4), 493-498.
[] [PMID: 7629743]
Elzoghby, A.O.; Samy, W.M.; Elgindy, N.A. Albumin-based nanoparticles as potential controlled release drug delivery systems. J. Control. Release, 2012, 157(2), 168-182.
[] [PMID: 21839127]
Kratz, F. Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles. J. Control. Release, 2008, 132(3), 171-183.
[] [PMID: 18582981]
Nosrati, H.; Salehiabar, M.; Afroogh, S. Bovine serum albumin: An efficient biomacromolecule nanocarrier for improve therapeutic efficacy of chrysin. J. Mol. Liq., 2018, 271, 639-646.
Nosrati, H.; Abbasi, R.; Charmi, J.; Rakhshbahar, A.; Aliakbarzadeh, F.; Danafar, H.; Davaran, S. Folic acid conjugated bovine serum albumin: An efficient smart and tumor targeted biomacromolecule for inhibition folate receptor positive cancer cells. Int. J. Biol. Macromol., 2018, 117, 1125-1132.
[] [PMID: 29885392]
Desai, N. Nanoparticle albumin bound (nab) technology: targeting tumors through the endothelial gp60 receptor and SPARC. Abstr. Nanotechnology. Biol. Med., 2007, 2007(3), 337-346.
Kim, T.H.; Jiang, H.H.; Youn, Y.S.; Park, C.W.; Tak, K.K.; Lee, S.; Kim, H.; Jon, S.; Chen, X.; Lee, K.C. Preparation and characterization of water-soluble albumin-bound curcumin nanoparticles with improved antitumor activity. Int. J. Pharm., 2011, 403(1-2), 285-291.
[] [PMID: 21035530]
Figuerola, A.; Di Corato, R.; Manna, L.; Pellegrino, T. From iron oxide nanoparticles towards advanced iron-based inorganic materials designed for biomedical applications. Pharmacol. Res., 2010, 62(2), 126-143.
[] [PMID: 20044004]
Asmatulu, R.; Zalich, M.A.; Claus, R.O.; Riffle, J.S. Synthesis, characterization and targeting of biodegradable magnetic nanocomposite particles by external magnetic fields. J. Magn. Magn. Mater., 2005, 2018(292), 108-119.
Kouassi, G.K.; Irudayaraj, J. Magnetic and gold-coated magnetic nanoparticles as a DNA sensor. Anal. Chem., 2006, 78(10), 3234-3241.
[] [PMID: 16689521]
Tamer, U.; Gundogdu, Y.; Boyaci, I.H.; Pekmez, K. Synthesis of magnetic core - shell Fe3O4 - Au nanoparticle for biomolecule immobilization and detection. J. Nanopart. Res., 2010, 12, 1187-1196.
Shen, Z.; Li, Y.; Kohama, K.; Oneill, B.; Bi, J. Improved drug targeting of cancer cells by utilizing actively targetable folic acid-conjugated albumin nanospheres. Pharmacol. Res., 2011, 63(1), 51-58.
[] [PMID: 21035550]
Reyes-Ortega, F.; Delgado, Á.V.; Schneider, E.K.; Checa Fernández, B.L.; Iglesias, G.R. Magnetic nanoparticles coated with a thermosensitive polymer with hyperthermia properties. Polymers (Basel), 2017, 10(1), 1-15.
[] [PMID: 30966044]
Pan, B.F.; Gao, F.; Gu, H.C. Dendrimer modified magnetite nanoparticles for protein immobilization. J. Colloid Interface Sci., 2005, 284(1), 1-6.
[] [PMID: 15752777]
Grassi-Schultheiss, P.P.; Heller, F.; Dobson, J. Analysis of magnetic material in the human heart, spleen and liver. Biometals, 1997, 10(4), 351-355.
[] [PMID: 9353885]
Chen, J.; Yang, P.; Ma, Y.; Wu, T. Characterization of chitosan magnetic nanoparticles for in situ delivery of tissue plasminogen activator. Carbohydr. Polym., 2011, 2011(84), 364-372.
Olivier, J.C.; Fenart, L.; Chauvet, R.; Pariat, C.; Cecchelli, R.; Couet, W. Indirect evidence that drug brain targeting using polysorbate 80-coated polybutylcyanoacrylate nanoparticles is related to toxicity. Pharm. Res., 1999, 16(12), 1836-1842.
[] [PMID: 10644071]
Doolaanea, A.A.; Mansor, N.I.; Mohd Nor, N.H.; Mohamed, F. Co-encapsulation of Nigella sativa oil and plasmid DNA for enhanced gene therapy of Alzheimer’s disease. J. Microencapsul., 2016, 33(2), 114-126.
[] [PMID: 26982435]
Kumagai, A.K.; Eisenberg, J.B.; Pardridge, W.M. Absorptive-mediated endocytosis of cationized albumin and a β-endorphin-cationized albumin chimeric peptide by isolated brain capillaries. Model system of blood-brain barrier transport. J. Biol. Chem., 1987, 262(31), 15214-15219.
[PMID: 2959663]
Broadwell, R.D. Transcytosis of macromolecules through the blood-brain barrier: A cell biological perspective and critical appraisal. Acta Neuropathol., 1989, 79(2), 117-128.
[] [PMID: 2688350]
Jin, J.; Bae, K.H.; Yang, H.; Lee, S.J.; Kim, H.; Kim, Y.; Joo, K.M.; Seo, S.W.; Park, T.G.; Nam, D.H. In vivo specific delivery of c-Met siRNA to glioblastoma using cationic solid lipid nanoparticles. Bioconjug. Chem., 2011, 22(12), 2568-2572.
[] [PMID: 22070554]
Masserini, M. Nanoparticles for brain drug delivery. ISRN Biochem., 2013.2013238428
[] [PMID: 25937958]
Michaelis, K.; Hoffmann, M.M.; Dreis, S.; Herbert, E.; Alyautdin, R.N.; Michaelis, M.; Kreuter, J.; Langer, K. Covalent linkage of apolipoprotein e to albumin nanoparticles strongly enhances drug transport into the brain. J. Pharmacol. Exp. Ther., 2006, 317(3), 1246-1253.
[] [PMID: 16554356]
Croy, J.E.; Brandon, T.; Komives, E.A. Two apolipoprotein E mimetic peptides, ApoE(130-149) and ApoE(141-155)2, bind to LRP1. Biochemistry, 2004, 43(23), 7328-7335.
[] [PMID: 15182176]
Kreuter, J. Influence of the surface properties on nanoparticle-mediated transport of drugs to the brain. J. Nanosci. Nanotechnol., 2004, 4(5), 484-488.
[] [PMID: 15503433]
Wankhede, M.; Bouras, A.; Kaluzova, M.; Hadjipanayis, C.G. Magnetic nanoparticles: an emerging technology for malignant brain tumor imaging and therapy. Expert Rev. Clin. Pharmacol., 2012, 5(2), 173-186.
[] [PMID: 22390560]
Chertok, B.; Moffat, B.A.; David, A.E.; Yu, F.; Bergemann, C.; Ross, B.D.; Yang, V.C. Iron oxide nanoparticles as a drug delivery vehicle for MRI monitored magnetic targeting of brain tumors. Biomaterials, 2008, 29(4), 487-496.
[] [PMID: 17964647]
Alyautdin, R.N.; Petrov, V.E.; Langer, K.; Berthold, A.; Kharkevich, D.A.; Kreuter, J. Delivery of loperamide across the blood-brain barrier with polysorbate 80-coated polybutylcyanoacrylate nanoparticles. Pharm. Res., 1997, 14(3), 325-328.
[] [PMID: 9098875]

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Article Details

Year: 2019
Published on: 28 August, 2019
Page: [698 - 711]
Pages: 14
DOI: 10.2174/1567201816666190828153017
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