Targeted delivery of nano-therapeutics for major disorders of the central nervous system

Pharmaceutical Research

Volumn 30, Issue 10, 2013, Pages 2485-2498

  Gao, Huile ^a   Pang, Zhiqing ^a   Jiang, Xinguo ^a  

^a FUDAN UNIVERSITY   (China)

Author keywords

brain tumor; central nervous system; cerebrovascular disease; neurodegenerative disorder; targeted delivery

Indexed keywords

ACETYLCHOLINE; ACLARUBICIN; AMYLOID BETA PROTEIN ANTIBODY; BRAIN DERIVED NEUROTROPHIC FACTOR; CURCUMIN; DEFEROXAMINE; DOCETAXEL; DOXORUBICIN; ERLOTINIB; FIBROBLAST GROWTH FACTOR 1; FIBROBLAST GROWTH FACTOR 2; GINSENOSIDE RB 1; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; HIGH MOBILITY GROUP B1 PROTEIN; LAPATINIB; LIPOSOME; NANOCOATING; NC 1900; PACLITAXEL; RECOMBINANT ERYTHROPOIETIN; RIVASTIGMINE; SUPEROXIDE DISMUTASE; TAMOXIFEN; TEMOZOLOMIDE; UNCLASSIFIED DRUG; UROCORTIN; VASCULOTROPIN; VASOACTIVE INTESTINAL POLYPEPTIDE; VASOPRESSIN DERIVATIVE;

ALZHEIMER DISEASE; BLOOD BRAIN BARRIER; BRAIN ISCHEMIA; BRAIN METASTASIS; BRAIN TUMOR; BREAST TUMOR; CANCER CHEMOTHERAPY; CEREBROVASCULAR ACCIDENT; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DELIVERY SYSTEM; DRUG EFFICACY; DRUG HALF LIFE; DRUG PENETRATION; DRUG TARGETING; HUMAN; INTRACRANIAL DRUG ADMINISTRATION; LOW DRUG DOSE; MEMORY DISORDER; MULTIPLE CYCLE TREATMENT; NANOENCAPSULATION; NANOPHARMACEUTICS; NANOTECHNOLOGY; NEUROPROTECTION; NONHUMAN; PARKINSON DISEASE; PRIORITY JOURNAL; REVIEW; TREATMENT PLANNING;

ANIMALS; BLOOD-BRAIN BARRIER; CENTRAL NERVOUS SYSTEM AGENTS; CENTRAL NERVOUS SYSTEM DISEASES; DRUG CARRIERS; DRUG DELIVERY SYSTEMS; HUMANS; NANOPARTICLES; NEUROPROTECTIVE AGENTS; PHARMACEUTICAL PREPARATIONS;

EID: 84883858762     PISSN: 07248741     EISSN: 1573904X     Source Type: Journal    
DOI: 10.1007/s11095-013-1122-4     Document Type: Review

References (151)

1. Wohlfart S, Gelperinaand S, Kreuter J. Transport of drugs across the blood-brain barrier by nanoparticles. J Control Release. 2012;161:264-73.
2. Begley DJ. Delivery of therapeutic agents to the central nervous system: the problems and the possibilities. Pharmacol Ther. 2004;104:29-45.
3. Brasnjevic I, Steinbusch HW, Schmitz C, Martinez-Martinez P. Delivery of peptide and protein drugs over the blood-brain barrier. Prog Neurobiol. 2009;87:212-51.
4. Pardridge WM. CNS drug design based on principles of blood-brain barrier transport. J Neurochem. 1998;70:1781-92.
5. Pardridge WM. Drug targeting to the brain. Pharm Res. 2007;24:1733-44.
6. Guo L, Renand J, Jiang X. Perspectives on brain-targeting drug delivery systems. Curr Pharm Biotechnol. 2012;13:2310-8.
7. Srikanthand M, Kessler JA. Nanotechnology-novel therapeutics for CNS disorders. Nat Rev Neurol. 2012;8:307-18.
8. Liuand Y, Lu W. Recent advances in brain tumor-targeted nano-drug delivery systems. Expert Opin Drug Deliv. 2012;9:671-86.
9. Ricard D, Idbaih A, Ducray F, Lahutte M, Hoang-Xuan K, Delattre JY. Primary brain tumours in adults. Lancet. 2012;379:1984-96.
10. Allhenn D, Boushehriand MA, Lamprecht A. Drug delivery strategies for the treatment of malignant gliomas. Int J Pharm. 2012;436:299-310.
11. Agarwal S, Sane R, Oberoi R, Ohlfest JR, Elmquist WF. Delivery of molecularly targeted therapy to malignant glioma, a disease of the whole brain. Expert Rev Mol Med. 2011;13:e17.
12. Bidrosand DS, Vogelbaum MA. Novel drug delivery strategies in neuro-oncology. Neurotherapeutics. 2009;6:539-46.
13. Clarke J, Butowskiand N, Chang S. Recent advances in therapy for glioblastoma. Arch Neurol. 2010;67:279-83.
14. Wolburg H, Noell S, Fallier-Becker P, Mack AF, Wolburg-Buchholz K. The disturbed blood-brain barrier in human glioblastoma. Mol Aspects Med. 2012;33:579-89.
15. Agarwal S, Manchanda P, Vogelbaum MA, Ohlfest JR, Elmquist WF. Function of the blood-brain barrier and restriction of drug delivery to invasive glioma cells: findings in an orthotopic rat xenograft model of glioma. Drug Metab Dispos. 2013;41:33-9.
16. Bronger H, Konig J, Kopplow K, Steiner HH, Ahmadi R, Herold-Mende C, et al. ABCC drug efflux pumps and organic anion uptake transporters in human gliomas and the blood-tumor barrier. Cancer Res. 2005;65:11419-28.
17. Groothuis DR. The blood-brain and blood-tumor barriers: a review of strategies for increasing drug delivery. Neuro Oncol. 2000;2:45-59.
18. Roberts WG, Delaat J, Nagane M, Huang S, Cavenee WK, Palade GE. Host microvasculature influence on tumor vascular morphology and endothelial gene expression. Am J Pathol. 1998;153:1239-48.
19. Zhanand C, Lu W. The blood-brain/tumor barriers: challenges and chances for malignant gliomas targeted drug delivery. Curr Pharm Biotechnol. 2012;13:2380-7.
20. Hobbs SK, Monsky WL, Yuan F, Roberts WG, Griffith L, Torchilin VP, et al. Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. Proc Natl Acad Sci U S A. 1998;95:4607-12.
21. Sarin H, Kanevsky AS, Wu H, Sousa AA, Wilson CM, Aronova MA, et al. Physiologic upper limit of pore size in the blood-tumor barrier of malignant solid tumors. J Transl Med. 2009;7:51.
22. Sarin H, Kanevsky AS, Wu H, Brimacombe KR, Fung SH, Sousa AA, et al. Effective transvascular delivery of nanoparticles across the blood-brain tumor barrier into malignant glioma cells. J Transl Med. 2008;6:80.
23. Mohri M, Nittaand H, Yamashita J. Expression of multidrug resistance-associated protein (MRP) in human gliomas. J Neurooncol. 2000;49:105-15.
24. Fattori S, Becherini F, Cianfriglia M, Parenti G, Romanini A, Castagna M. Human brain tumors: multidrug-resistance P-glycoprotein expression in tumor cells and intratumoral capillary endothelial cells. Virchows Arch. 2007;451:81-7.
25. Taskar KS, Rudraraju V, Mittapalli RK, Samala R, Thorsheim HR, Lockman J, et al. Lapatinib distribution in HER2 overexpressing experimental brain metastases of breast cancer. Pharm Res. 2012;29:770-81.
26. Pang Z, Gao H, Yu Y, Guo L, Chen J, Pan S, et al. Enhanced intracellular delivery and chemotherapy for glioma rats by transferrin-conjugated biodegradable polymersomes loaded with Doxorubicin. Bioconjug Chem. 2011;22:1171-80.
27. Pang Z, Lu W, Gao H, Hu K, Chen J, Zhang C, et al. Preparation and brain delivery property of biodegradable polymersomes conjugated with OX26. J Control Release. 2008;128:120-7.
28. Zhan C, Li B, Hu L, Wei X, Feng L, Fu W, et al. Micelle-based brain-targeted drug delivery enabled by a nicotine acetylcholine receptor ligand. Angew Chem Int Ed Engl. 2011;50:5482-5.
29. Gaillard PJ, Visser CC, Appeldoorn CCM, Rip J. Enhanced brain drug delivery: safely crossing the blood-brain barrier. Drug Discov Today Technol. 2012;9:e155-60.
30. Lu W, Wan J, Zhang Q, She Z, Jiang X. Aclarubicin-loaded cationic albumin-conjugated pegylated nanoparticle for glioma chemotherapy in rats. Int J Cancer. 2007;120:420-31.
31. Lu W, Sun Q, Wan J, She Z, Jiang XG. Cationic albumin-conjugated pegylated nanoparticles allow gene delivery into brain tumors via intravenous administration. Cancer Res. 2006;66:11878-87.
32. Gao H, Pang Z, Pan S, Cao S, Yang Z, Chen C, et al. Anti-glioma effect and safety of docetaxel-loaded nanoemulsion. Arch Pharm Res. 2012;35:333-41.
33. Hovanessian AG, Soundaramourty C, El KD, Nondier I, Svab J, Krust B. Surface expressed nucleolin is constantly induced in tumor cells to mediate calcium-dependent ligand internalization. PLoS One. 2010;5:e15787.
34. Maletinska L, Blakely EA, Bjornstad KA, Deen DF, Knoff LJ, Forte TM. Human glioblastoma cell lines: levels of low-density lipoprotein receptor and low-density lipoprotein receptor-related protein. Cancer Res. 2000;60:2300-3.
35. Zhang YF, Wang JC, Bian DY, Zhang X, Zhang Q. Targeted delivery of RGD-modified liposomes encapsulating both combretastatin A-4 and doxorubicin for tumor therapy: in vitro and in vivo studies. Eur J Pharm Biopharm. 2010;74:467-73.
36. Huang R, Ke W, Han L, Li J, Liu S, Jiang C. Targeted delivery of chlorotoxin-modified DNA-loaded nanoparticles to glioma via intravenous administration. Biomaterials. 2011;32:2399-406.
37. Mamot C, Drummond DC, Noble CO, Kallab V, Guo Z, Hong K, et al. Epidermal growth factor receptor-targeted immunoliposomes significantly enhance the efficacy of multiple anticancer drugs in vivo. Cancer Res. 2005;65:11631-8.
38. Iresonand CR, Kelland LR. Discovery and development of anticancer aptamers. Mol Cancer Ther. 2006;5:2957-62.
39. Guo J, Gao X, Su L, Xia H, Gu G, Pang Z, et al. Aptamer-functionalized PEG-PLGA nanoparticles for enhanced anti-glioma drug delivery. Biomaterials. 2011;32:8010-20.
40. Gao H, Qian J, Yang Z, Pang Z, Xi Z, Cao S, et al. Whole-cell SELEX aptamer-functionalised poly(ethyleneglycol)-poly(epsilon-caprolactone) nanoparticles for enhanced targeted glioblastoma therapy. Biomaterials. 2012;33:6264-72.
41. Gu G, Xia H, Hu Q, Liu Z, Jiang M, Kang T, et al. PEG-co-PCL nanoparticles modified with MMP-2/9 activatable low molecular weight protamine for enhanced targeted glioblastoma therapy. Biomaterials. 2013;34:196-208.
42. Jiang T, Olson ES, Nguyen QT, Roy M, Jennings PA, Tsien RY. Tumor imaging by means of proteolytic activation of cell-penetrating peptides. Proc Natl Acad Sci U S A. 2004;101:17867-72.
43. Kuai R, Yuan W, Li W, Qin Y, Tang J, Yuan M, et al. Targeted delivery of cargoes into a murine solid tumor by a cell-penetrating peptide and cleavable poly(ethylene glycol) comodified liposomal delivery system via systemic administration. Mol Pharm. 2011;8:2151-61.
44. Kuai R, Yuan W, Qin Y, Chen H, Tang J, Yuan M, et al. Efficient delivery of payload into tumor cells in a controlled manner by TAT and thiolytic cleavable PEG co-modified liposomes. Mol Pharm. 2010;7:1816-26.
45. Sawant RM, Hurley JP, Salmaso S, Kale A, Tolcheva E, Levchenko TS, et al. "SMART" drug delivery systems: double-targeted pH-responsive pharmaceutical nanocarriers. Bioconjug Chem. 2006;17:943-9.
46. Xu H, Deng Y, Chen D, Hong W, Lu Y, Dong X. Esterase-catalyzed dePEGylation of pH-sensitive vesicles modified with cleavable PEG-lipid derivatives. J Control Release. 2008;130:238-45.
47. Guo L, Fan L, Pang Z, Ren J, Ren Y, Li J, et al. TRAIL and doxorubicin combination enhances anti-glioblastoma effect based on passive tumor targeting of liposomes. J Control Release. 2011;154:93-102.
48. Zhan C, Wei X, Qian J, Feng L, Zhu J, Lu W. Co-delivery of TRAIL gene enhances the anti-glioblastoma effect of paclitaxel in vitro and in vivo. J Control Release. 2012;160:630-6.
49. Schottelius M, Laufer B, Kessler H, Wester HJ. Ligands for mapping alphavbeta3-integrin expression in vivo. Acc Chem Res. 2009;42:969-80.
50. Sun X, Pang Z, Ye H, Qiu B, Guo L, Li J, et al. Co-delivery of pEGFP-hTRAIL and paclitaxel to brain glioma mediated by an angiopep-conjugated liposome. Biomaterials. 2012;33:916-24.
51. Li J, Feng L, Fan L, Zha Y, Guo L, Zhang Q, et al. Targeting the brain with PEG-PLGA nanoparticles modified with phage-displayed peptides. Biomaterials. 2011;32:4943-50.
52. Gao H, Qian J, Cao S, Yang Z, Pang Z, Pan S, et al. Precise glioma targeting of and penetration by aptamer and peptide dual-functioned nanoparticles. Biomaterials. 2012;33:5115-23.
53. Xu Q, Liu Y, Su S, Li W, Chen C, Wu Y. Anti-tumor activity of paclitaxel through dual-targeting carrier of cyclic RGD and transferrin conjugated hyperbranched copolymer nanoparticles. Biomaterials. 2012;33:1627-39.
54. Li Y, He H, Jia X, Lu WL, Lou J, Wei Y. A dual-targeting nanocarrier based on poly(amidoamine) dendrimers conjugated with transferrin and tamoxifen for treating brain gliomas. Biomaterials. 2012;33:3899-908.
55. Zhang P, Hu L, Yin Q, Feng L, Li Y. Transferrin-modified c[RGDfK]-paclitaxel loaded hybrid micelle for sequential blood-brain barrier penetration and glioma targeting therapy. Mol Pharm. 2012;9:1590-8.
56. Nie Y, Schaffert D, Rodl W, Ogris M, Wagner E, Gunther M. Dual-targeted polyplexes: one step towards a synthetic virus for cancer gene therapy. J Control Release. 2011;152:127-34.
57. Ying X, Wen H, Lu WL, Du J, Guo J, Tian W, et al. Dual-targeting daunorubicin liposomes improve the therapeutic efficacy of brain glioma in animals. J Control Release. 2010;141:183-92.
58. He H, Li Y, Jia XR, Du J, Ying X, Lu WL, et al. PEGylated Poly(amidoamine) dendrimer-based dual-targeting carrier for treating brain tumors. Biomaterials. 2011;32:478-87.
59. Du J, Lu WL, Ying X, Liu Y, Du P, Tian W, et al. Dual-targeting topotecan liposomes modified with tamoxifen and wheat germ agglutinin significantly improve drug transport across the blood-brain barrier and survival of brain tumor-bearing animals. Mol Pharm. 2009;6:905-17.
60. Kakimoto S, Moriyama T, Tanabe T, Shinkai S, Nagasaki T. Dual-ligand effect of transferrin and transforming growth factor alpha on polyethyleneimine-mediated gene delivery. J Control Release. 2007;120:242-9.
61. Ito S, Ohtsukiand S, Terasaki T. Functional characterization of the brain-to-blood efflux clearance of human amyloid-beta peptide (1-40) across the rat blood-brain barrier. Neurosci Res. 2006;56:246-52.
62. Liand H, Qian ZM. Transferrin/transferrin receptor-mediated drug delivery. Med Res Rev. 2002;22:225-50.
63. Demeule M, Regina A, Che C, Poirier J, Nguyen T, Gabathuler R, et al. Identification and design of peptides as a new drug delivery system for the brain. J Pharmacol Exp Ther. 2008;324:1064-72.
64. Ke W, Shao K, Huang R, Han L, Liu Y, Li J, et al. Gene delivery targeted to the brain using an Angiopep-conjugated polyethyleneglycol-modified polyamidoamine dendrimer. Biomaterials. 2009;30:6976-85.
65. Xin H, Sha X, Jiang X, Zhang W, Chen L, Fang X. Anti-glioblastoma efficacy and safety of paclitaxel-loading Angiopep-conjugated dual targeting PEG-PCL nanoparticles. Biomaterials. 2012;33:8167-76.
66. Re F, Gregoriand M, Masserini M. Nanotechnology for neurodegenerative disorders. Nanomedicine. 2012;8 Suppl 1:S51-8.
67. Tanifum EA, Dasgupta I, Srivastava M, Bhavane RC, Sun L, Berridge J, et al. Intravenous delivery of targeted liposomes to amyloid-beta pathology in APP/PSEN1 transgenic mice. PLoS One. 2012;7:e48515.
68. Tanziand RE, Bertram L. Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective. Cell. 2005;120:545-55.
69. Santacruz K, Lewis J, Spires T, Paulson J, Kotilinek L, Ingelsson M, et al. Tau suppression in a neurodegenerative mouse model improves memory function. Science. 2005;309:476-81.
70. Brendza RP, Bacskai BJ, Cirrito JR, Simmons KA, Skoch JM, Klunk WE, et al. Anti-Abeta antibody treatment promotes the rapid recovery of amyloid-associated neuritic dystrophy in PDAPP transgenic mice. J Clin Invest. 2005;115:428-33.
71. Zhou QH, Fu A, Boado RJ, Hui EK, Lu JZ, Pardridge WM. Receptor-mediated abeta amyloid antibody targeting to Alzheimer's disease mouse brain. Mol Pharm. 2011;8:280-5.
72. Chauhan NB, Davisand F, Xiao C. Wheat germ agglutinin enhanced cerebral uptake of anti-Abeta antibody after intranasal administration in 5XFAD mice. Vaccine. 2011;29:7631-7.
73. Ono K, Hasegawa K, Naiki H, Yamada M. Curcumin has potent anti-amyloidogenic effects for Alzheimer's beta-amyloid fibrils in vitro. J Neurosci Res. 2004;75:742-50.
74. Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, et al. Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem. 2005;280:5892-901.
75. Mourtas S, Canovi M, Zona C, Aurilia D, Niarakis A, La Ferla B, et al. Curcumin-decorated nanoliposomes with very high affinity for amyloid-beta1-42 peptide. Biomaterials. 2011;32:1635-45.
76. Mathew A, Fukuda T, Nagaoka Y, Hasumura T, Morimoto H, Yoshida Y, et al. Curcumin loaded-PLGA nanoparticles conjugated with Tet-1 peptide for potential use in Alzheimer's disease. PLoS One. 2012;7:e32616.
77. Taylor M, Moore S, Mourtas S, Niarakis A, Re F, Zona C, et al. Effect of curcumin-associated and lipid ligand-functionalized nanoliposomes on aggregation of the Alzheimer's Abeta peptide. Nanomedicine. 2011;7:541-50.
78. Mulik RS, Monkkonen J, Juvonen RO, Mahadik KR, Paradkar AR. ApoE3 mediated poly(butyl) cyanoacrylate nanoparticles containing curcumin: study of enhanced activity of curcumin against beta amyloid induced cytotoxicity using in vitro cell culture model. Mol Pharm. 2010;7:815-25.
79. Liu JK, Teng Q, Garrity-Moses M, Federici T, Tanase D, Imperiale MJ, et al. A novel peptide defined through phage display for therapeutic protein and vector neuronal targeting. Neurobiol Dis. 2005;19:407-18.
80. Brambilla D, Le Droumaguet B, Nicolas J, Hashemi SH, Wu LP, Moghimi SM, et al. Nanotechnologies for Alzheimer's disease: diagnosis, therapy, and safety issues. Nanomedicine. 2011;7:521-40.
81. Cui Z, Lockman PR, Atwood CS, Hsu CH, Gupte A, Allen DD, et al. Novel D-penicillamine carrying nanoparticles for metal chelation therapy in Alzheimer's and other CNS diseases. Eur J Pharm Biopharm. 2005;59:263-72.
82. Yang Z, Zhang Y, Yang Y, Sun L, Han D, Li H, et al. Pharmacological and toxicological target organelles and safe use of single-walled carbon nanotubes as drug carriers in treating Alzheimer disease. Nanomedicine. 2010;6:427-41.
83. Kreuter J. Nanoparticulate systems for brain delivery of drugs. Adv Drug Deliv Rev. 2001;47:65-81.
84. Wilson B, Samanta MK, Santhi K, Kumar KP, Paramakrishnan N, Suresh B. Poly(n-butylcyanoacrylate) nanoparticles coated with polysorbate 80 for the targeted delivery of rivastigmine into the brain to treat Alzheimer's disease. Brain Res. 2008;1200:159-68.
85. Joshi SA, Chavhanand SS, Sawant KK. Rivastigmine-loaded PLGA and PBCA nanoparticles: preparation, optimization, characterization, in vitro and pharmacodynamic studies. Eur J Pharm Biopharm. 2010;76:189-99.
86. Mamiyaand T, Ukai M. [Gly(14)]-Humanin improved the learning and memory impairment induced by scopolamine in vivo. Br J Pharmacol. 2001;134:1597-9.
87. Yu Y, Pang Z, Lu W, Yin Q, Gao H, Jiang X. Self-assembled polymersomes conjugated with lactoferrin as novel drug carrier for brain delivery. Pharm Res. 2012;29:83-96.
88. Li J, Zhang C, Li J, Fan L, Jiang X, Chen J, et al. Brain delivery of NAP with PEG-PLGA nanoparticles modified with phage display peptides. Pharm Res. 2013;30:1813-23.
89. Mishima K, Tsukikawa H, Miura I, Inada K, Abe K, Matsumoto Y, et al. Ameliorative effect of NC-1900, a new AVP4-9 analog, through vasopressin V1A receptor on scopolamine-induced impairments of spatial memory in the eight-arm radial maze. Neuropharmacology. 2003;44:541-52.
90. Wu H, Huand K, Jiang X. From nose to brain: understanding transport capacity and transport rate of drugs. Expert Opin Drug Deliv. 2008;5:1159-68.
91. Gao X, Wu B, Zhang Q, Chen J, Zhu J, Zhang W, et al. Brain delivery of vasoactive intestinal peptide enhanced with the nanoparticles conjugated with wheat germ agglutinin following intranasal administration. J Control Release. 2007;121:156-67.
92. Gao X, Tao W, Lu W, Zhang Q, Zhang Y, Jiang X, et al. Lectin-conjugated PEG-PLA nanoparticles: preparation and brain delivery after intranasal administration. Biomaterials. 2006;27:3482-90.
93. Li J, Wu H, Hong J, Xu X, Yang H, Wu B, et al. Odorranalectin is a small peptide lectin with potential for drug delivery and targeting. PLoS One. 2008;3:e2381.
94. Wu H, Li J, Zhang Q, Yan X, Guo L, Gao X, et al. A novel small Odorranalectin-bearing cubosomes: preparation, brain delivery and pharmacodynamic study on amyloid-beta(2)(5)(-)(3)(5)-treated rats following intranasal administration. Eur J Pharm Biopharm. 2012;80:368-78.
95. Denyerand R, Douglas MR. Gene therapy for Parkinson's disease. Parkinsons Dis. 2012;2012:757305.
96. Macpheeand GJ, Carson A. Impulse control disorders in Parkinson disease: is cognitive-behavioral therapy worth a wager? Neurology. 2013;80:782-3.
97. Reddy P, Martinez-Martin P, Rizos A, Martin A, Faye GC, Forgacs I, et al. Intrajejunal levodopa versus conventional therapy in Parkinson disease: motor and nonmotor effects. Clin Neuropharmacol. 2012;35:205-7.
98. Soler R, Fullhase C, Hanson A, Campeau L, Santos C, Andersson KE. Stem cell therapy ameliorates bladder dysfunction in an animal model of Parkinson disease. J Urol. 2012;187:1491-7.
99. Alonso-Frech F, Sanahujaand JJ, Rodriguez AM. Exercise and physical therapy in early management of Parkinson disease. Neurologist. 2011;17:S47-53.
100. Ronand D, Janak PH. GDNF and addiction. Rev Neurosci. 2005;16:277-85.
101. Zhou QH, Boado RJ, Lu JZ, Hui EK, Pardridge WM. Monoclonal antibody-glial-derived neurotrophic factor fusion protein penetrates the blood-brain barrier in the mouse. Drug Metab Dispos. 2010;38:566-72.
102. Abuirmeileh A, Lever R, Kingsbury AE, Lees AJ, Locke IC, Knight RA, et al. The corticotrophin-releasing factor-like peptide urocortin reverses key deficits in two rodent models of Parkinson's disease. Eur J Neurosci. 2007;26:417-23.
103. Hu K, Li J, Shen Y, Lu W, Gao X, Zhang Q, et al. Lactoferrin-conjugated PEG-PLA nanoparticles with improved brain delivery: in vitro and in vivo evaluations. J Control Release. 2009;134:55-61.
104. Hu K, Shi Y, Jiang W, Han J, Huang S, Jiang X. Lactoferrin conjugated PEG-PLGA nanoparticles for brain delivery: preparation, characterization and efficacy in Parkinson's disease. Int J Pharm. 2011;415:273-83.
105. Wen Z, Yan Z, Hu K, Pang Z, Cheng X, Guo L, et al. Odorranalectin- conjugated nanoparticles: preparation, brain delivery and pharmacodynamic study on Parkinson's disease following intranasal administration. J Control Release. 2011;151:131-8.
106. Zhang Y, Calon F, Zhu C, Boado RJ, Pardridge WM. Intravenous nonviral gene therapy causes normalization of striatal tyrosine hydroxylase and reversal of motor impairment in experimental parkinsonism. Hum Gene Ther. 2003;14:1-12.
107. Gonzalez-Barrios JA, Lindahl M, Bannon MJ, Anaya-Martinez V, Flores G, Navarro-Quiroga I, et al. Neurotensin polyplex as an efficient carrier for delivering the human GDNF gene into nigral dopamine neurons of hemiparkinsonian rats. Mol Ther. 2006;14:857-65.
108. Martinez-Fong D, Bannon MJ, Trudeau LE, Gonzalez-Barrios JA, Arango-Rodriguez ML, Hernandez-Chan NG, et al. NTS-Polyplex: a potential nanocarrier for neurotrophic therapy of Parkinson's disease. Nanomedicine. 2012;8:1052-69.
109. Huang R, Ke W, Liu Y, Jiang C, Pei Y. The use of lactoferrin as a ligand for targeting the polyamidoamine-based gene delivery system to the brain. Biomaterials. 2008;29:238-46.
110. Huang R, Han L, Li J, Ren F, Ke W, Jiang C, et al. Neuroprotection in a 6-hydroxydopamine-lesioned Parkinson model using lactoferrin-modified nanoparticles. J Gene Med. 2009;11:754-63.
111. Huang J, Liu H, Gu W, Yan Z, Xu Z, Yang Y, et al. A delivery strategy for rotenone microspheres in an animal model of Parkinson's disease. Biomaterials. 2006;27:937-46.
112. Sindhu KM, Saravananand KS, Mohanakumar KP. Behavioral differences in a rotenone-induced hemiparkinsonian rat model developed following intranigral or median forebrain bundle infusion. Brain Res. 2005;1051:25-34.
113. Huang R, Ke W, Liu Y, Wu D, Feng L, Jiang C, et al. Gene therapy using lactoferrin-modified nanoparticles in a rotenone-induced chronic Parkinson model. J Neurol Sci. 2010;290:123-30.
114. Andersonand JT, Robertson NP. Risk factors and cerebrovascular disease. J Neurol. 2013;260:692-4.
115. Cooke MJ, Wang Y, Morshead CM, Shoichet MS. Controlled epi-cortical delivery of epidermal growth factor for the stimulation of endogenous neural stem cell proliferation in stroke-injured brain. Biomaterials. 2011;32:5688-97.
116. Gupta A, Nair S, Schweitzer AD, Kishore S, Johnson CE, Comunale JP, et al. Neuroimaging of cerebrovascular disease in the aging brain. Aging Dis. 2012;3:414-25.
117. Elger B, Gieseler M, Schmuecker O, Schumann I, Seltz A, Huth A. Extended therapeutic time window after focal cerebral ischemia by non-competitive inhibition of AMPA receptors. Brain Res. 2006;1085:189-94.
118. Wuand D, Pardridge WM. Neuroprotection with noninvasive neurotrophin delivery to the brain. Proc Natl Acad Sci U S A. 1999;96:254-9.
119. Zhangand Y, Pardridge WM. Conjugation of brain-derived neurotrophic factor to a blood-brain barrier drug targeting system enables neuroprotection in regional brain ischemia following intravenous injection of the neurotrophin. Brain Res. 2001;889:49-56.
120. Pardridge WM. Blood-brain barrier drug targeting enables neuroprotection in brain ischemia following delayed intravenous administration of neurotrophins. Adv Exp Med Biol. 2002;513:397-430.
121. Wu D. Neuroprotection in experimental stroke with targeted neurotrophins. NeuroRx. 2005;2:120-8.
122. Song BW, Vinters HV, Wu D, Pardridge WM. Enhanced neuroprotective effects of basic fibroblast growth factor in regional brain ischemia after conjugation to a blood-brain barrier delivery vector. J Pharmacol Exp Ther. 2002;301:605-10.
123. D'Agnilloand F, Alayash AI. Site-specific modifications and toxicity of blood substitutes. The case of diaspirin cross-linked hemoglobin. Adv Drug Deliv Rev. 2000;40:199-212.
124. Conover CD, Linberg R, Shum KL, Shorr RG. The ability of polyethylene glycol conjugated bovine hemoglobin (PEG-Hb) to adequately deliver oxygen in both exchange transfusion and top-loaded rat models. Artif Cells Blood Substit Immobil Biotechnol. 1999;27:93-107.
125. Lee J, Lee J, Yoon S, Nho K. Pharmacokinetics of 125I-radiolabelled PEG-hemoglobin SB1. Artif Cells Blood Substit Immobil Biotechnol. 2006;34:277-92.
126. Ji HJ, Chai HY, Nahm SS, Lee J, Bae GW, Nho K, et al. Neuroprotective effects of the novel polyethylene glycol-hemoglobin conjugate SB1 on experimental cerebral thromboembolism in rats. Eur J Pharmacol. 2007;566:83-7.
127. Reddyand MK, Labhasetwar V. Nanoparticle-mediated delivery of superoxide dismutase to the brain: an effective strategy to reduce ischemia-reperfusion injury. FASEB J. 2009;23:1384-95.
128. Erlandsson A, Lin CH, Yu F, Morshead CM. Immunosuppression promotes endogenous neural stem and progenitor cell migration and tissue regeneration after ischemic injury. Exp Neurol. 2011;230:48-57.
129. Kolb B, Morshead C, Gonzalez C, Kim M, Gregg C, Shingo T, et al. Growth factor-stimulated generation of new cortical tissue and functional recovery after stroke damage to the motor cortex of rats. J Cereb Blood Flow Metab. 2007;27:983-97.
130. Wang Y, Cooke MJ, Lapitsky Y, Wylie RG, Sachewsky N, Corbett D, et al. Transport of epidermal growth factor in the stroke-injured brain. J Control Release. 2011;149:225-35.
131. Wang Y, Cooke MJ, Morshead CM, Shoichet MS. Hydrogel delivery of erythropoietin to the brain for endogenous stem cell stimulation after stroke injury. Biomaterials. 2012;33:2681-92.
132. Sun Y, Jin K, Xie L, Childs J, Mao XO, Logvinova A, et al. VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia. J Clin Invest. 2003;111:1843-51.
133. Zhao H, Bao XJ, Wang RZ, Li GL, Gao J, Ma SH, et al. Postacute ischemia vascular endothelial growth factor transfer by transferrin-targeted liposomes attenuates ischemic brain injury after experimental stroke in rats. Hum Gene Ther. 2011;22:207-15.
134. Kim JB, Sig CJ, Yu YM, Nam K, Piao CS, Kim SW, et al. HMGB1, a novel cytokine-like mediator linking acute neuronal death and delayed neuroinflammation in the postischemic brain. J Neurosci. 2006;26:6413-21.
135. Kim ID, Lim CM, Kim JB, Nam HY, Nam K, Kim SW, et al. Neuroprotection by biodegradable PAMAM ester (e-PAM-R)-mediated HMGB1 siRNA delivery in primary cortical cultures and in the postischemic brain. J Control Release. 2010;142:422-30.
136. Budihardjo I, Oliver H, Lutter M, Luo X, Wang X. Biochemical pathways of caspase activation during apoptosis. Annu Rev Cell Dev Biol. 1999;15:269-90.
137. Al-Jamal KT, Gherardini L, Bardi G, Nunes A, Guo C, Bussy C, et al. Functional motor recovery from brain ischemic insult by carbon nanotube-mediated siRNA silencing. Proc Natl Acad Sci U S A. 2011;108:10952-7.
138. Lee J, Hyun H, Kim J, Ryu JH, Kim HA, Park JH, et al. Dexamethasone-loaded peptide micelles for delivery of the heme oxygenase-1 gene to ischemic brain. J Control Release. 2012;158:131-8.
139. Yu YP, Xu QQ, Zhang Q, Zhang WP, Zhang LH, Wei EQ. Intranasal recombinant human erythropoietin protects rats against focal cerebral ischemia. Neurosci Lett. 2005;387:5-10.
140. Wang ZL, Cheng SM, Ma MM, Ma YP, Yang JP, Xu GL, et al. Intranasally delivered bFGF enhances neurogenesis in adult rats following cerebral ischemia. Neurosci Lett. 2008;446:30-5.
141. Hanson LR, Roeytenberg A, Martinez PM, Coppes VG, Sweet DC, Rao RJ, et al. Intranasal deferoxamine provides increased brain exposure and significant protection in rat ischemic stroke. J Pharmacol Exp Ther. 2009;330:679-86.
142. Jiang Y, Wei N, Lu T, Zhu J, Xu G, Liu X. Intranasal brain-derived neurotrophic factor protects brain from ischemic insult via modulating local inflammation in rats. Neuroscience. 2011;172:398-405.
143. Cheng X, Wang Z, Yang J, Ma M, Lu T, Xu G, et al. Acidic fibroblast growth factor delivered intranasally induces neurogenesis and angiogenesis in rats after ischemic stroke. Neurol Res. 2011;33:675-80.
144. Lu T, Jiang Y, Zhou Z, Yue X, Wei N, Chen Z, et al. Intranasal ginsenoside Rb1 targets the brain and ameliorates cerebral ischemia/reperfusion injury in rats. Biol Pharm Bull. 2011;34:1319-24.
145. Kim ID, Shin JH, Lee HK, Jin YC, Lee JK. Intranasal delivery of HMGB1-binding heptamer peptide confers a robust neuroprotection in the postischemic brain. Neurosci Lett. 2012;525:179-83.
146. Zhu J, Jiang Y, Wu L, Lu T, Xu G, Liu X. Suppression of local inflammation contributes to the neuroprotective effect of ginsenoside Rb1 in rats with cerebral ischemia. Neuroscience. 2012;202:342-51.
147. Kim ID, Shin JH, Kim SW, Choi S, Ahn J, Han PL, et al. Intranasal delivery of HMGB1 siRNA confers target gene knockdown and robust neuroprotection in the postischemic brain. Mol Ther. 2012;20:829-39.
148. Liu L, Venkatraman SS, Yang YY, Guo K, Lu J, He B, et al. Polymeric micelles anchored with TAT for delivery of antibiotics across the blood-brain barrier. Biopolymers. 2008;90:617-23.
149. Fazil M, Md S, Haque S, Kumar M, Baboota S, Sahni JK, et al. Development and evaluation of rivastigmine loaded chitosan nanoparticles for brain targeting. Eur J Pharm Sci. 2012;47:6-15.
150. Ruan Y, Yao L, Zhang B, Zhang S, Guo J. Antinociceptive properties of nasal delivery of neurotoxin-loaded nanoparticles coated with polysorbate-80. Peptides. 2011;32:1526-9.
151. Ren T, Xu N, Cao C, Yuan W, Yu X, Chen J, et al. Preparation and therapeutic efficacy of polysorbate-80-coated amphotericin B/PLA-b-PEG nanoparticles. J Biomater Sci Polym Ed. 2009;20:1369-80.