Nose to brain delivery of nanoformulations for neurotherapeutics in parkinson’s disease: Defining the preclinical, clinical and toxicity issues

Current Drug Delivery

Volumn 13, Issue 8, 2016, Pages 1205-1221

  Pathak, Kamla ^a   Akhtar, Nida ^b  

^a Pharmacy College Saifai   (India)

^b NH 2   (India)

Author keywords

Nanoformulations; Neuro therapeutics; Nose to brain delivery; Parkinson s disease; Preclinical aspects

Indexed keywords

ANTIPARKINSON AGENT; CHITOSAN NANOPARTICLE; DENDRIMER; MULTIDRUG RESISTANCE PROTEIN; NANOCARRIER; POLYMER; SOLID LIPID NANOPARTICLE;

BLOOD BRAIN BARRIER; CENTRAL NERVOUS SYSTEM; CLINICAL EFFECTIVENESS; DRUG DEGRADATION; DRUG DELIVERY SYSTEM; DRUG FORMULATION; HUMAN; MICELLE; NANOEMULSION; NANOENCAPSULATION; NANOPHARMACEUTICS; NANOTECHNOLOGY; NONHUMAN; PARKINSON DISEASE; PRIORITY JOURNAL; REVIEW;

EID: 84995897700     PISSN: 15672018     EISSN: 18755704     Source Type: Journal    
DOI: 10.2174/1567201813666160607123409     Document Type: Review

References (133)

1. Kulkarni, A.D.; Vanjary, Y.H.; Sancheti, K.H.; Belgamwar, V.S.; Surana, S.J.; Pardeshi, C.V. Nanotechnology mediated nose to brain drug delivery for Parkinson’s disease: a mini review. J. Drug Target., 2015, 23, 775-788
2. Gabathuler, R. Approaches to transport therapeutic drugs across the blood-brain barrier to treat brain diseases. Neurobiol. Dis., 2010, 37, 48-57
3. Misra, A.; Ganesh, S.; Shahiwala, A.; Shah, S.P. Drug delivery to the central nervous system: a review. J. Pharm. Pharm. Sci., 2003, 6, 252-273
4. Roney, C.; Kulkarni, P.; Arora, V.; Antich, P.; Bonte, F.; Wu, A.; Mallikaarjuana, N.N.; Manohar, S.S.; Liang, H.F.; Kulkarni, H.F.; Sung, H.W.; Sairam, M.; Aminabhavi, T.M. Targeted Nanoparticles for drug delivery through the blood-brain barrier for Alzheimer’s disease. J. Control. Release., 2005, 108, 193-214
5. Pardeshi, C.V.; Rajput, P.V.; Belgamwar, V.S.; Tekade, A.R. Formulation, optimization and evaluation of spray-dried mucoadhesive microspheres as intranasal carriers for valsartan. J. Microencapsul., 2011, 29, 103-114
6. Bahadur, S.; Pathak, K. Physicochemical and physiological considerations for efficient nose-to-brain targeting. Expert. Opin. Drug. Deliv., 2012, 9, 19-31
7. Chen, J.; Wang, X.; Wang, J.; Liu, G.; Tang, X. Evaluation of brain-targeting for the nasal delivery of ergoloid mesylate by the microdialysis method in rats. Eur. J. Pharm. Biopharm., 2008, 68, 694-700
8. Ali, J.; Ali, M.; Baboota, S. Potential of nanoparticulate drug delivery systems by intranasal administration. Curr. Pharm. Res., 2010, 10, 1644-1653
9. Djupesland, P.G.; Messina, J.C.; Mahmoud, R.A. The nasal approach to delivering treatment for brain diseases: an anatomic, physiologic, and delivery technology overview. Ther. Deliv., 2014, 5, 709-733
10. Braak, H.; Bohl, J.R.; Muller, C.M.; Rub, U.; de Vos, R.A.; Del Tredici, K.; Stanley, Fahn. Lecture 2005: the staging procedure 647 for the inclusion body pathology associated with sporadic Parkinson’s disease reconsidered. Mov. Disord., 2006, 21, 2042-2051
11. Zigmond, M.J.; Burke, R.E. Pathophysiology of Parkinson’s disease; Davis, K.L.; Charney, D.; Coyle, J.T.; Nemeroff, C. Ed. Neuropsychopharmacology the fifth generation of progress. 5th ed. Brentwood, Tennessee: American College of Neuropsychopharmacology; Brentwood, 2002; pp.1781-1793
12. Hindle, H.V. Ageing, neurodegenration and Parkinson’s disease. Age Ageing, 2009, 39, 156-161
13. Cole, N.B.; Murphy, D.D. The cell biology of alpha-synuclein: a sticky problem? Neuromol. Med., 2002, 1, 95-109
14. de Lau, L.M.; Breteler, M.M. Epidemiology of Parkinson’s disease. Lancet Neurol., 2006, 5, 525-535
15. Freire, C.; Koifman, S. Pesticide exposure and Parkinson’s disease: epidemiological evidence of association. Neurotoxicol., 2012, 33, 947-971
16. Moretto, A.; Colosio, C. The role of pesticide exposure in the genesis of Parkinson’s disease: epidemiological studies and experimental data. Toxicology, 2013, 307, 24-34
17. Tanner, C.M.; Kamel, F.; Ross, G.W.; Hoppin, J.A.; Goldman, S.M.; Korell, M.; Marras, C.; Bhudhikanok, G.S.; Kasten, M.; Chade, A.R.; Comyns, K.; Richards, M.B.; Meng, C.; Priestley, B.; Fernandez, H.H.; Cambi, F.; Umbach, D.M.; Blair, A.; Sandler, D.P.; Langston, J.W. Rotenone, Paraquat and Parkinson’s Disease. Environ. Health Perspect., 2011, 119, 866-872
18. Samii, A.; Nutt, J.G.; Ransom, B.R. Parkinson’s disease. Lancet., 2004, 363, 1783-1793
19. Lesage, S.; Brice, A. Parkinson’s disease: from monogenic forms to genetic susceptibility factors. Hum. Mol. Genet., 2009, 18, 48-59
20. Davie, C.A. A review of Parkinson’s disease. Br. Med. Bull., 2008, 86, 109-127
21. Nalls, M.A.; Plagnol, V.; Hernandez, D.G.; Sharma, M.; Sheerin, U.M.; Saad, M.; Simon-Sanchez, J.; Schulte, C.; Lesage, S.; Sveinbjornsdottir, S.; Stefansson, K.; Martinez, M.; Hardy, J.; Heutink, P.; Brice, A.; Gasser, T.; Singleton, A.B.; Wood, N.W. Imputation of sequence variants for identification of genetic risks for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet., 2011, 377, 641-649
22. Schapira, A.H. Treatment options in the modern management of Parkinson disease. Arch. Neurol., 2007, 64, 1083-1088
23. www.rxlist.com/cycloset-drug.html [Accessed 13 May 2015]
24. www.rxlist.com/parlodel-drug.html [Accessed 13 May 2015]
25. www.accessdata.fda.gov [Accessed Feb 2008]
26. www.medicines.org.uk [Accessed 23 Dec 2013]
27. Houghton, D.; Hurtig, H.; Metz, S.; Brandabur, M. Parkinson’s Disease: Medication. 5th ed. National Parkinson Foundation, 200 SE First Street, Suite 800 Miami, Florida; 2014, pp. 1-76
28. www.drugs.com [Accessed 28 Apr 2015]
29. www.emsam.com [Accessed 13 May 2015]
30. www.rxlist.com/tasmar-drug.html [Accessed 13 May 2015]
31. Gaikwad, A.K. Transdermal drug delivery system: formulation aspects and evaluation. Comprehensive J. Pharm. Sci., 2013, 1, 1-10
32. Gendelman, H.E.; Ananthararm, V.; Bronich, T.; Ghaisas, S.; Jin, H.; Kanthasamy, A.G.; Liu, X.; McMillan, J.; Mosley, R.L.; Narasimhan, B.; Mallapragada, S.K. Nanoneutomedicines for degenerative, inflammatory and infectious nervous system diseases. Nanomed. Nanotech. Biol. Med., 2015, 11, 751-767
33. Azeem, A.; Ahmad, F.J.; Khar, R.K.; Talegaonkar, S. Nanocarrier for the transdermal delivery of antiparkinsonian drug. AAPS PharmSciTech., 2009, 10, 1093-1103
34. Darreh-Shori, T.; Jelic, V. Safety and tolerability of transdermal and oral rivastigmine in Alzheimer’s disease and Parkinson’s disease dementia. Opin. Drug Safety, 2010, 9, 167-176
35. Antonini, A.; Chaudhari, K.R.; Martinez-Martin, P.; Odin, P. Oral and infusion levodopa-based strategies for managing motor complications in patients with Parkinson’s disease. CNS Drugs, 2010, 24, 119-129
36. Arica, B.; Kas, S.H.; Moghdam, A.; Akalan, N.; Hincal, A.A. Carbidopa/Levodopa-loaded biodegradable microspheres: in vivo evaluation on experimental Parkinsonism in rats. J Control. Release, 2005, 102, 689-697
37. Tsai, M.J.; Huang, Y.B.; Wu, P.C.; Fu, Y.S.; Kao, Y.R.; Fang, J.Y.; Tsai, Y.S. Oral apomorphine delivery from solid lipid nanoparticles with different monostearate emulsifiers: pharmacokinetic and behavioural evaluations. J. Pharm. Sci., 2011, 100, 547-557
38. Hsu, S.H.; Wen, C.J.; Al-Suwayeh, S.A.; Chang, H.W.; Yen, T.C.; Fang, J.Y. Physicochemical characterization and in vivo bioluminescence imaging of nanostructured lipid carriers for targeting the brain: apomorphine as a model drug. Nanotechnology, 2010, 21, 1-9
39. Lloret, S.P.; Rascol, O. Ritogotine for the treatment of advanced Parkinson’s disease. Eur. Neurol. Rev., 2009, 4, 24-28
40. Sanford, M.; Scott, L.J. Spotlight on ritogotine transdermal patch in Parkinson’s disease. Drugs Aging, 2011, 28, 1015-1017
41. Mishra, A.D.; Patel, C.N.; Shah, D.R. Formulation and optimization of ethosomes for transdermal delivery of ropinirole hydrochloride. Curr. Drug Deliv., 2013, 10, 500-516
42. Bjorklund, T.; Kirik, D. Scientific rationale for the development of gene therapy strategies for Parkinson’s disease. Biochim. Biophys. Acta., 2009, 1792, 703-713
43. Wijeyekoon, R.; Barker RA. Cell replacement therapy for Parkinson’s disease. Biochim. Biophys. Acta., 2009, 1792, 688-702
44. Johnstone, D.M.; Coleman, K.; Moro, C.; Torres, N.; Eells, J.T.; Baker, G.E.; Ashkan, K., Stone, J., Benabid, A.L.; Mitrafanis, J. The potential of light therapy in parkinson’s disease. Chron. Physiol. Therap., 2014, 4, 1-14
45. Modi, G.; Pillay, V.; Choonara, Y.E.; Ndesendo, V.M.; du Toit, L.C.; Naidoo, D. Nanotechnological applications for the treatment of neurodegenerative disorders. Prog. Neurobiol., 2009, 88, 272-285
46. Pardeshi, C.V.; Belgamwar, V.S. Direct nose to brain drug delivery via integrated nerve pathways bypassing the blood-brain barrier: an excellent platform for brain targeting. Expert Opin. Drug Deliv., 2013, 10, 957-972
47. Wilson, B.; Samanta, M.K.; Santhi, K.; Kumar, K.P.; Ramasamy, M.; Suresh, B. Chitosan nanoparticles as a new delivery system for the anti-Alzheimer drug tacrine. Nanomedicine, 2009, 6, 144-152
48. Mistry, A.; Stolnik, S.; Illum, L. Nanoparticles for direct nose-tobrain delivery of drugs. Int. J. Pharm., 2009, 379, 146-157
49. Woensel, M.V.; Wauthoz, N.; Rosiere, R.; Amighi, K.; Mathieu, V.; Lefranc, F.; Van Gool, S.W.; de Vleesschouwer, S. Formulations for intranasal delivery of pharmacological agents to combat brain disease: a new opportunity to tackle GBM. Cancers, 2013, 5, 1020-1048
50. Patel, S.; Patel, B.; Patel, Z.; Pardeshi, C. Nanocarriers as Novel Nose-to-Brain Targeted Drug Delivery Platforms. Ind. J. Novel Drug Deliv., 2012, 4, 243-251
51. Kreuter, J. Nanoparticulate systems for brain delivery of drugs. Adv. Drug Deliv. Rev., 2001, 47, 65-81
52. Mohamed, F.; Walle, C.F.V. Engineering biodegradable polyester particles with specific drug targeting and drug release properties. J. Pharm. Sci., 2008, 97, 71-87
53. Csaba, N.; Garcia-Fuentes, M.; Alonso, M.J. The performance of nanocarriers for transmucosal drug delivery. Expert Opin. Drug. Del., 2006, 3, 463-78
54. Yadav, N.; Khatak, S.; Sara, U.V.S. Solid lipid nanoparticles-a review. Int. J. Appl. Pharm., 2013, 5, 8-18
55. Martinho, N.; Damge, C.; Reis, C.P. Recent Advances in Drug Delivery Systems. J. Biomaterials Nanobiotech., 2011, 2, 510-526
56. Prakash, R.T.U.; Thiagarajan, P. Nanoemulsions for drug delivery through different routes. Res. Biotech., 2011, 2, 1-13
57. Jayaraj, R.L.; Chandramohan, V.; Namasivayam, E. Nanomedicines for parkinson disease: current status and future perspective. Int. J. Pharm. Biol. Sci., 2013, 4, 692-704
58. Lovelyn, C.; Attama, A.A. Current State of Nanoemulsions in Drug Delivery. J. Biomater. Nanobiotech., 2011, 2, 626-639
59. Lawrence, M.J.; Rees, G.D. Microemulsion based media as a novel drug 868 delivery system. Adv. Drug Deliv. Rev., 2000, 45, 89-121
60. Gavini, E.; Hegge, A.B.; Rassu, G.; Sanna, V.; Testa, C.; Pirisino, G.; Karlsen, J.; Giunchedi, P. Nasal administration of carbamazepine using chitosan microspheres: In vitro/in vivo studies. Int. J. Pharm., 2006, 7, 9-15
61. Kumar, M.; Misra, A.; Pathak, K. Formulation and characterization of Nanoemulsion of olanzapine for intranasal delivery. PDA J. Pharm. Sci. Tech., 2009, 63, 501-511
62. Kumar, M.; Pathak, K.; Misra, A. Formulation and characterization of nanoemulsion-based drug delivery system of risperidone. Drug Dev. Ind. Pharm., 2009, 35, 387-395
63. Bahadur, S.; Pathak, K. Buffered nanoemulsion for nose to brain delivery of ziprasidone hydrochloride: Preformulation and pharmacodynamic evaluation. Curr. Drug Deliv., 2012, 9, 1-12
64. Mustafa, G.; Baboota, S.; Ahuja, A.; Ali, J. Formulation development of chitosan coated intranasal ropinirole nanoemulsion for better management option of Parkinson: an in vitro ex vivo evaluation. Curr. Nanosci., 2014, 3, 348-60
65. Joseph, E.; Saha, R.N. Advances in Brain Targeted Drug Delivery: Nanoparticulate Systems. J. Pharm. Sci. Tech., 2013, 3, 1-8
66. Olivier, J.C. Drug transport to brain with targeted nanoparticles. NeuroRx Pharm., 2005, 2, 108-119
67. Snehalatha, M.; Venugopal, K.; Saha, R.N.; Babbar, A.K.; Sharma, R.K. Etoposide loaded PLGA and PCL Nanoparticles II: Biodistribution and pharmacokinetics after radiolableling with Tc-99m. Drug Del., 2008, 5, 277-287
68. Gambaryan, B.Y.; Kondrasheva, I.G.; Severin, E.S.; Guseva, A.A.; Kamensky, A.A. Increasing the Efficiency of Parkinson’s Disease Treatment Using a poly (lactic-co-glycolic acid) (PLGA) Based LDOPA Delivery System. Exp. Neorobiol., 2014, 23, 246-252
69. Patil, G.B.; Surana, S.J. Fabrication and statistical optimization of surface engineered PLGA nanoparticles for naso-brain delivery of ropinirole hydrochloride: in vivo-ex vivo studies. J. Biomat. Sci., 2013, 24, 1740-56
70. Sadigh-Eteghad, S.; Talebi, M.; Farhoudi, M.; Mahmoudi, J.; Reyhani, B. Effects of Levodopa loaded chitosan nanoparticles on cell viability and caspase-3 expression in PC12 neural like cells. Neuroscience, 2013, 18, 281-283
71. Md, S.; Khan, R.A.; Mustafa, G.; Chuttani, K.; Baboota, S.; Sahni, J.K.; Ali, J. Bromocriptine loaded chitosan nanoparticles intended for direct nose to brain delivery: Pharmacodynamic, Pharmacokinetic and scintigraphy study in mice model. Eur. J. Pharm. Biopharm., 2013, 48, 393-405
72. Md, S.; Haque, S.; Fazil, M.; Kumar, M.; Baboota, S.; Sahni, J.K.; Ali, J. Optimised nanoformulation of bromocriptine for direct nose-to-brain delivery: biodistribution, pharmacokinetic and dopamine estimation by ultra-HPLC/mass spectrometry method. Expert Opin. Drug Deliv., 2014, 11, 827-842
73. Sharma, S.; Lohan, S.; Murthy, R.S.R. Formulation and characterization of intranasal mucoadhesive nanoparticulates and thermoreversible gel of levodopa for brain delivery. Drug Dev. Ind. Pharm., 2014, 40, 869-878
74. Jafarieh, O.; Md, S.; Ali, M. Design, characterization and evaluation of intranasal delivery of ropinirole-loaded mucoadhesive nanoparticles for brain targeting. Drug Dev. Ind. Pharm., 2014, 11, 1-8
75. Gulati, N.; Nagaich, U.; Saraf, S. Fabrication and in vitro characterization of polymeric nanoparticles for Parkinson’s therapy: a novel approach. Braz. J. Pharm. Sci., 2014, 50, 869-876
76. Mittal, D.; Md, S.; Hasan, Q.; Fazil, M.; Ali, A.; Baboota, S.; Ali, J. Brain targeted nanoparticulate drug delivery system of rasagiline via inranasal route. Drug. Deliv., 2016, 23(1), 130-139
77. Ekambaram, P.; Sathali, A.A.H.; Kumar, P. Solid lipid nanoparticles: a review. Sci. Rev. Chem. Commun., 2012, 2, 80-102
78. Mudshinge, S.R.; Deore, A.B.; Patil, S.; Bhalgat, C.M. Nanoparticles: emerging carriers for drug delivery. Saudi. Pharm. J., 2011, 19, 129-141
79. Tzachev, C.T.; Svilenov, H.L. Lipid Nanoparticles at the Current Stage and Prospects -A Review Article. Int. J. Pharm. Sci. Rev. Res., 2013, 18, 103-115
80. Pardeshi, C.V.; Rajput, P.V.; Belgamwar, B.S.; Tekade, A.R.; Surane, SJ. Novel surface modified solid lipid nanoparticles as intranasal carriers for ropinirole hydrochloride: application of factorial design approach. Drug Deliv., 2013, 20, 47-56
81. Mustafa, G.; Ahuja, A.; Baboota, S. Nose to brain drug delivery of modified solid-lipid nanoparticle bearing ropinirole: an in vitro evaluation. Antiviral Res., 2011, 92, 408-414
82. Kunasekaran, V.; Krishnamoorthy, K. Compatibility studies of rasagiline mesylate with selected excipients for an effective solid lipid nanoparticles formulation. Int. J. Pharm. Pharm. Sci., 2015, 7, 73-80
83. Wissing, S.A.; Kayser, O.; Muller, R.H. Solid lipid nanoparticles for parenteral drug delivery. Adv. Drug Deliv. Rev., 2004, 56, 1257-1272
84. Jaiswal, P.; Gidwani, B.; Vyas, A. Nanostructured lipid carriers and their current application in targeted drug delivery. Artif. Cells Nanomed. Biotechnol., 2016, 44(1), 27-40
85. Liu, K.S.; Wen, C.J.; Yen, T.C.; Sung, K.C.; Ku, M.C.; Wang, J.J.; Fang, J.Y. Combined strategies of apomorphine diester progrugs and nanostructured lipid carriers for efficient brain targeting. Nanotechnology, 2012, 223(9), 095103
86. Wong, H.L.; Bendayan, R.; Rauth, A.M.; Wu, X.Y. Simultaneous delivery of doxorubicin and GG918 (Elacridar) by new Polymer-Lipid Hybrid Nanoparticles (PLN) for enhanced treatment of multidrug-resistant breast cancer. J. Control. Release, 2006, 116, 275-284
87. Geral, C.; Angelova, A.; Lesieur, S. From molecular to nanotechnology strategies for delivery of neurotrophins: emphasis on brainderived neurotrophic factor (BDNF). Pharmaceutics, 2013, 5(1), 127-67
88. Angelova, A.; Angelov, B.; Drechsler, M.; Lesieur, S. Neurotrophin delivery using nanotechnology. Drug Disc. Today, 2013, 18, 1263-1271
89. Angelova, A.; Angelov, B.; Drechsler, M.; Garamus, V.M.; Lesieur, S. Protein entrapment in PEGylated lipid nanoparticles. Int. J. Pharm., 2013, 454, 625-632
90. Angelov, B.; Angelova, A.; Filippov, S.; Drechsler, M.; Stepanek, P.; Lesieur, S. Multicompartment lipid cubic nanoparticles with high protein upload: Millisecond dynamics of formation. ACS Nano., 2014, 8, 5216-5226
91. Angelova, A.; Angelov, B.; Mutafchieva, R.; Lesieur, S.; Couvreur, P. Self-assembled liquid crystalline lipid carriers for protein, peptide, and nucleic acid drug delivery. Acc. Chem. Res., 2011, 44, 147-156
92. Angelov, B.; Angelova, A.; Filippov, S.; Karlsson, G.; Terrill, N.; Lesieur, S.; Stepanek, P. Topology and internal structure of PEGylated lipid nanocarriers for neuronal transfection: Synchrotron radiation SAXS and cryo-TEM studies. Soft Matter., 2011, 7, 9714-9720
93. Mulla, N.S. Novel sustained release formulation of levodopadendrimer conjugate. Creighton University, School of Pharmacy and Health Professions, 2011, pp. 1-105
94. Jayaraj, R.L.; Chandramohan, V.; Namasivayam, E. Nanomedicines for parkinson disease: current status and future perspective. Int. J. Pharma. Bio. Sci., 2013, 4, 692-704
95. Jain, R.; Nabar, S.; Dandekar, P.; Patravale, V. Micellar nanocarriers: potential nose-to-brain delivery of zolmitriptan as novel migraine therapy. Pharm. Res., 2010, 4, 655-664
96. Aly, A.E.; Waszczak, B.L. Intranasal gene delivery for treating Parkinson’s disease: overcoming the blood brain barrier. Expert Opin. Drig Deliv., 2015, 12, 1923-1941
97. Kim, I.D.; Shin, J.H.; Kim, S.W.; Choi, S.; Ahn, J.; Han, P.L.; Park, J.S.; Lee, J.K. Intranasal delivery of HMGB1 siRNA confers target gene knockdown and robust neuroprotection in the postischemic brain. Mol. Ther., 2012, 20, 829-839
98. Harmon, B.T.; Aly, A.T.; Padegimas, L.; Sesenoglu-Laird, O.; Cooper, M.J.; Waszczak, B.L. Intranasal administration of plasmid DNA nanopar-ticles yields successful transfection and expression of a reporterprotein in rat brain. Gene Ther., 2014, 21, 514-521
99. Newland B.; Dowd, E.; Pandit, A. Biomaterial approaches to gene therapies for neurodegenerative disorders of the CNS. Biomater. Sci., 2013, 1, 556-576
100. Kanazawa T, Akiyama, F., Kakizaki, S., Takashima, Y., Seta, Y. 2013. Delivery of siRNA to the brain using a combination of noseto-brain delivery and cell-penetrating peptide-modified nanomicelles. Biomaterials, 2013, 34, 9220-9226
101. Yacoubian, T.A.; Standaert, D.G. Targets for neuroprotection in Parkinson’s disease. Biochim. Biophys. Acta., 2009, 1792, 676-687
102. Dawson, T.; Dawson, V. Neuroprotective and neurorestorative strategies for Parkinson’s disease. Nat. Neurosci., 2002, 5, 1058-1061
103. Newland, B.; Newland, H.; Werner, C.; Rosser, A.; Wang, W. Prospects for polymer therapeutics in Parkinson’s diseaseand other neurodegenerative disorders. Prog. Polym. Sci., 2015, 44, 79-112
104. Obeso, J.A.; Rodriguez-Oroz, M.C.; Goetz, C.G.; Marin, C.; Kordower, J.H.; Rodriquez, M.; Hirsch, E.C.; Farrer, M.; Schapira, A.H.; Halliday, G. Missing pieces in the Parkinson’s disease puzzle. Nat. Med., 2010, 16, 653-661
105. Yakoubian, T.A.; Standaert, D.G. Targets for neuroprotection in Parkinson’s disease. Biochim. Biophys. Acta, 2009, 1792, 676-687
106. Olanow, W.C.; Bartus, R.T.; Baumann, T.L.; Factor, S.; Boulis, N.; Stacy, M.; Turner, D.A.; Marks, W.; Larson, P.; Starr, P.A.; Jankovic, J.; Simpson, R.; Watts, R.; Guthrie, B.; Poston, K.; Henderson, J.M.; Stern, M.; Baltuch, G.; Goetz, C.G.; Herzog, C.; Jeffrey, H.; Alterman, R.; Lozano, A.M.; Lang, A.E. Gene delivery of neurturin to putamen and substantia nigra in Parkinson disease: A double-blind, randomized, controlled trial. Ann. Neurolog., 2015, 78, 248-257
107. Yadav, H.P.; Li, Y. The development of treatment for Parkinson’s disease. Adv Parkinson’s Dis., 2015, 4, 59-78
108. Nunes, A.; Al-Jamal, K.T.; Kostarelos, K. Therapeutics, imaging and toxicity of nanomaterials in the central nervous system. J. Control. Release, 2012, 161, 290-306
109. Ulbrich, K.; Hekmatara, T.; Herbert, E.; Kreuter, J. Transferrinand transferrin-891 receptor antibody-modified nanoparticles enable drug delivery across the blood-brain barrier (BBB). Eur. J. Pharm. Biopharm., 2009, 71, 251-256
110. Cupaioli, F.A.; Zucca, F.A.; Boraschi, D.; Zecca, L. Engineered nanoparticles. How friendly is this new guest. Progr. Neurobiol., 2014, 119, 20-38
111. Mahmoudi, M.; Laurent, S.; Shokrgozar, M.A.; Hosseinkhani, M. Toxicity evaluations of superparamagnetic iron oxide nanoparticles: cell vision versus physicochemical properties of nanoparticles. ACS Nano., 2011, 5, 7263-7276
112. Hutter, E.; Boridy, S.; Labrecque, S.; Lalancette-Hebert, M.; Kriz, J.; Winnik, F.M.; Maysinger, D. Microglial response to gold nanoparticles. ACS Nano., 2010, 4, 2595-2606
113. Zhang, L.; Bai, R.; Li, B.; Cuicui, G.; Jiangfeng, D.; Ying, L.; Guyader, L.L.; Zhao, Y.; Wu, Y.; He, S.; Ma, Y.; Chen, C. Rutile TiO2 particles exert size and surface coating dependent retention and lesions on the murine brain. Toxicol. Lett., 2011, 207, 73-81
114. Born, J.; Lange, T.; Kern, W.; Mcgregor, G.P.; Bickel, U.; Fehm, H.L. Sniffing neuropeptides: a transnasal approach to the human brain. Nat. Neurosci., 2002, 5, 514-516
115. Garbayo, E.; Ansorena, E.; Blanco-Prieto, M.J. Drug development in Parkinson’s disease: From emerging molecules to innovative drug delivery systems. Maturitas., 2013, 76, 272-278
116. www.clinicaltrials.gov [Accessed 10 Oct 2014]
117. www.abbvie.com [Accessed 12 Jan 2015]
118. www.acorda.com [Accessed 5 May 2015]
119. www.synagile.com [Accessed Dec 17 2013]
120. www.qrpharma.com [Accessed 06 Jan 2015]
121. www.impaxpharma.com [Accessed 08 Jan 2015]
122. www.usworldmeds.com [Accessed 13 Aug 2010]
123. www.merz.com [Accessed 09 Jan 2013]
124. Schapira, A.H.V. Monoamine oxidase-B inhibitors for the treatment of Parkinson’s disease: a review of symptomatic and potential disease-modifying effects. CNS Drugs, 2011, 25, 1061-1071
125. Castro-Caldas, A.; Delwaide, P.; Jost, W.; Merello, M.; Williams, A.; Lamberti, P.; Aguilar, M.; Del Signore, S.; Cesaro, P. Parkinson-Control Study Group. The Parkinson-control study: A 1-year randomized, double-blind trail comparing piribedil (150 mg/day) with bromocriptine (25 mg/day) in early combination with levodopa in Parkinson’s disease. Mov. Disord., 2006, 21, 500-509
126. 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, 273-283
127. Pillay, V.; Akilo, O.D.; Choonara, Y.E.; Kumar, P.; du Toit, L.C. Nose-to-Brain Neurotherapeutic Interventions. Adv. Neurother. Deliv. Tech., 2014, 2, 15-32
128. Grassin-Delyle, S.; Buenestado, A.; Naline, E.; Faisy, C.; Blouquit-Laye, S.; Couderc, L.J.; Le Guen, M.; Fischler, M.; Devillier, P. Intranasal drug delivery: an efficient and non-invasive route for systemic administration: focus on opioids. Pharmacol. Ther., 2012, 134, 366-379
129. Arora, P.; Sharma, S.; Garg, S. Permeability issues in nasal drug delivery. Drug Discov. Today, 2002, 7, 967-975
130. Fliegauf, M.; Sonnen, A.F.; Kremer, B.; Henneke, P. Mucociliary clearance defects in a murine in vitro model of pneumococcal airway infection. PLoS One, 2013, 8, e599525
131. Dominguez, A.; Alvarez, A.; Hilario, E.; Suarez-Merino, B.; Gonide-Cerio, F. Central nervous system diseases and the role of the blood-brain barrier in their treatment. Neurosci. Disc., 2013, 10, 114-125
132. Johnson, N.J.; Hanson, L.R.; Frey, W.H. Trigeminal pathways deliver a low molecular weight drug from the nose to the brain and orofacial structures. Mol. Pharm., 2010, 7, 884-893
133. Haney, M.J.; Zhao, Y.; Li, S.; Higginbotham, S.M.; Booth, S.L.; Han, H.Y.; Vetro, J.A.; Mosley, R.L.; Kabanov, A.V.; Gendelman, H.E.; Batrakova, E.V. Cell-mediated transfer of catalase nanoparticles from macrophages to brain endothelial, glial and neuronal cells. Nanomedicine, 2011, 6, 1215-30