title: Nanotechnology for CNS delivery of bio-therapeutic agents.
abstract: The current therapeutic strategies are not efficient in treating disorders related to the central nervous system (CNS) and have only shown partial alleviation of symptoms, as opposed to, disease modifying effects. With change in population demographics, the incidence of CNS disorders, especially neurodegenerative diseases, is expected to rise dramatically. Current treatment regimens are associated with severe side-effects, especially given that most of these are chronic therapies and involve elderly population. In this review, we highlight the challenges and opportunities in delivering newer and more effective bio-therapeutic agents for the treatment of CNS disorders. Bio-therapeutics like proteins, peptides, monoclonal antibodies, growth factors, and nucleic acids are thought to have a profound effect on halting the progression of neurodegenerative disorders and also provide a unique function of restoring damaged cells. We provide a review of the nano-sized formulation-based drug delivery systems and alternate modes of delivery, like the intranasal route, to carry bio-therapeutics effectively to the brain.
authors.affiliation: Department of Pharmaceutical Sciences School of Pharmacy Northeastern University Boston, MA 02115.
authors.forename: Lipa
authors.initials: L
authors.lastname: Shah
authors.forename: Sunita
authors.initials: S
authors.lastname: Yadav
authors.forename: Mansoor
authors.initials: M
authors.lastname: Amiji
keywords: Central nervous system; bio-therapeutics; blood-brain barrier; drug delivery; intranasal delivery; nano-sized formulations; olfactory receptor neurons; systemic delivery
references.citation: Pharm Res. 2003 Aug;20(8):1225-30
references.pmid: 12948020
references.citation: Exp Brain Res. 1986;63(3):461-73
references.pmid: 3758265
references.citation: Vaccine. 2001 Aug 14;19(31):4519-25
references.pmid: 11483279
references.citation: Adv Drug Deliv Rev. 2012 May 15;64(7):686-700
references.pmid: 22100125
references.citation: Biochem Pharmacol. 2012 Mar 1;83(5):559-66
references.pmid: 22051078
references.citation: Curr Drug Deliv. 2005 Oct;2(4):297-310
references.pmid: 16305433
references.citation: J Pharm Sci. 2004 Aug;93(8):1993-2008
references.pmid: 15236449
references.citation: Eur J Pharm Sci. 2000 Jul;11(1):1-18
references.pmid: 10913748
references.citation: Mol Pharm. 2013 May 6;10(5):1533-41
references.pmid: 22934681
references.citation: Mol Cell Neurosci. 2004 Oct;27(2):85-131
references.pmid: 15485768
references.citation: Brain. 2008 Dec;131(Pt 12):3311-34
references.pmid: 19015157
references.citation: Expert Opin Drug Deliv. 2011 May;8(5):581-603
references.pmid: 21391862
references.citation: Cancer. 2007 Feb 15;109(4):751-60
references.pmid: 17211866
references.citation: Int J Pharm. 2008 Jan 22;347(1-2):93-101
references.pmid: 17651927
references.citation: Nature. 1999 Jul 8;400(6740):173-7
references.pmid: 10408445
references.citation: J Drug Target. 2008 Jan;16(1):73-8
references.pmid: 18172823
references.citation: J Pharmacol Exp Ther. 2006 Jun;317(3):1246-53
references.pmid: 16554356
references.citation: Biochem Biophys Res Commun. 2006 Feb 24;340(4):1085-90
references.pmid: 16403441
references.citation: Acta Neuropathol. 1991;82(6):516-9
references.pmid: 1723831
references.citation: Mol Ther. 2003 Dec;8(6):886-94
references.pmid: 14664790
references.citation: J Pharm Pharmacol. 1995 May;47(5):379-81
references.pmid: 7494186
references.citation: Drug Deliv. 2012 Apr;19(3):149-54
references.pmid: 22353012
references.citation: Curr Drug Deliv. 2006 Apr;3(2):219-32
references.pmid: 16611008
references.citation: Biomaterials. 2008 Apr;29(10):1509-17
references.pmid: 18155137
references.citation: Brain Res. 1995 May 22;680(1-2):196-206
references.pmid: 7663977
references.citation: Pharm Res. 2004 Feb;21(2):201-30
references.pmid: 15032302
references.citation: Pharm Res. 2004 Jan;21(1):43-9
references.pmid: 14984256
references.citation: Neurosci Lett. 2004 May 6;361(1-3):128-31
references.pmid: 15135910
references.citation: Int J Pharm. 2007 Aug 1;340(1-2):207-15
references.pmid: 17499948
references.citation: Hum Gene Ther. 2003 Jan 1;14(1):1-12
references.pmid: 12573054
references.citation: J Pharmacol Exp Ther. 2006 Feb;316(2):647-53
references.pmid: 16293715
references.citation: Expert Opin Drug Deliv. 2009 Mar;6(3):211-25
references.pmid: 19290842
references.citation: Rejuvenation Res. 2011 Feb;14(1):3-16
references.pmid: 21291297
references.citation: Adv Drug Deliv Rev. 1998 Jan 5;29(1-2):117-133
references.pmid: 10837583
references.citation: Mol Membr Biol. 2010 Oct;27(7):260-73
references.pmid: 20929336
references.citation: Mol Pharm. 2009 May-Jun;6(3):928-39
references.pmid: 19278222
references.citation: Endocrinology. 2006 May;147(5):2088-94
references.pmid: 16469809
references.citation: J Pharmacol Exp Ther. 1995 Dec;275(3):1647-55
references.pmid: 8531140
references.citation: J Stroke Cerebrovasc Dis. 2004 Jan-Feb;13(1):16-23
references.pmid: 17903945
references.citation: Adv Drug Deliv Rev. 1999 Apr 5;36(2-3):299-321
references.pmid: 10837722
references.citation: J Pharm Sci. 2005 Jun;94(6):1187-95
references.pmid: 15858850
references.citation: J Pharm Pharmacol. 1994 May;46(5):378-9
references.pmid: 8083811
references.citation: J Pharmacol Exp Ther. 2004 May;309(2):469-75
references.pmid: 14724226
references.citation: J Drug Target. 2002 Jun;10(4):327-35
references.pmid: 12164381
references.citation: Clin J Pain. 1998 Mar;14(1):4-16
references.pmid: 9535309
references.citation: Discov Med. 2006 Aug;6(34):139-43
references.pmid: 17234133
references.citation: Neuroscience. 2004;127(2):481-96
references.pmid: 15262337
references.citation: J Pharm Sci. 2009 Jul;98(7):2501-15
references.pmid: 19025760
references.citation: J Pharm Pharmacol. 2004 Jan;56(1):3-17
references.pmid: 14979996
references.citation: Nat Rev Neurosci. 2006 Jan;7(1):41-53
references.pmid: 16371949
references.citation: Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):3-26
references.pmid: 11259830
references.citation: Brain Res Brain Res Protoc. 2000 Apr;5(2):135-9
references.pmid: 10775832
references.citation: Cancer Chemother Pharmacol. 1997;40 Suppl:S13-9
references.pmid: 9272128
references.citation: J Control Release. 2007 Aug 28;121(3):156-67
references.pmid: 17628165
references.citation: J Pharm Sci. 2010 Apr;99(4):1745-61
references.pmid: 19774660
references.citation: J Pharmacol Exp Ther. 1997 Sep;282(3):1541-6
references.pmid: 9316870
references.citation: Curr Drug Discov Technol. 2011 Jun;8(2):87-101
references.pmid: 21513485
references.citation: ChemMedChem. 2012 Mar 5;7(3):375-84
references.pmid: 22307951
references.citation: Expert Opin Drug Deliv. 2009 Oct;6(10):1017-32
references.pmid: 19732031
references.citation: Int J Pharm. 2007 Aug 16;341(1-2):20-5
references.pmid: 17482780
references.citation: Pharm Res. 2011 Mar;28(3):456-71
references.pmid: 20924653
references.citation: Gene Ther. 1995 Aug;2(6):418-23
references.pmid: 7584117
references.citation: Nat Neurosci. 2002 Jun;5(6):514-6
references.pmid: 11992114
references.citation: J Drug Target. 2010 Apr;18(3):179-90
references.pmid: 19807216
references.citation: J Pharm Sci. 2010 Apr;99(4):1654-73
references.pmid: 19877171
references.citation: Pharm Res. 2005 Jan;22(1):86-93
references.pmid: 15771234
references.citation: Front Biosci (Landmark Ed). 2011 Jan 01;16:1388-412
references.pmid: 21196238
references.citation: Science. 1992 Sep 18;257(5077):1698-700
references.pmid: 1529356
references.citation: Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):14164-9
references.pmid: 8943078
references.citation: J Neurochem. 2008 Aug;106(4):1534-44
references.pmid: 18489712
references.citation: Bioconjug Chem. 2008 Jul;19(7):1327-38
references.pmid: 18547095
references.citation: Eur J Pharm Sci. 2001 May;13(2):179-85
references.pmid: 11297902
references.citation: J Pharm Pharmacol. 2002 Jul;54(7):945-50
references.pmid: 12162713
references.citation: Nature. 2007 Jul 5;448(7149):39-43
references.pmid: 17572664
references.citation: Brain Res Bull. 2007 Sep 28;74(4):271-7
references.pmid: 17720549
references.citation: Amino Acids. 2006 Jun;30(4):351-67
references.pmid: 16622600
references.citation: Med Devices (Auckl). 2008 Jul;1:41-7
references.pmid: 22915907
references.citation: FASEB J. 2005 Mar;19(3):311-30
references.pmid: 15746175
references.citation: Int J Pharm. 2009 Sep 8;379(1):146-57
references.pmid: 19555750
references.citation: J Pharm Sci. 2007 Mar;96(3):473-83
references.pmid: 17117404
references.citation: Int J Pharm. 2006 Jul 6;317(1):40-6
references.pmid: 16631329
references.citation: Adv Drug Deliv Rev. 2007 Jul 10;59(6):491-504
references.pmid: 17532091
references.citation: J Pharm Sci. 1986 Nov;75(11):1085-8
references.pmid: 3102719
references.citation: Neurosci Lett. 2005 Oct 14;387(1):5-10
references.pmid: 16054296
references.citation: Neurosci Lett. 2012 Apr 4;513(2):193-7
references.pmid: 22387067
references.citation: Adv Drug Deliv Rev. 2007 Jul 10;59(6):454-77
references.pmid: 17570559
references.citation: Int J Pharm. 2007 Jun 7;337(1-2):1-24
references.pmid: 17475423
references.citation: FASEB J. 2011 Sep;25(9):3208-18
references.pmid: 21593432
references.citation: Neurosci Lett. 2009 Jan 9;449(2):108-11
references.pmid: 18996442
references.citation: J Pharmacol Exp Ther. 1996 Oct;279(1):77-83
references.pmid: 8858978
references.citation: J Neuroimmunol. 2004 Jun;151(1-2):66-77
references.pmid: 15145605
references.citation: Adv Drug Deliv Rev. 2012 Jul;64(10):943-52
references.pmid: 22210135
references.citation: Adv Drug Deliv Rev. 1998 Jan 5;29(1-2):13-38
references.pmid: 10837578