经鼻给药治疗中枢神经系统疾病的途径和潜力的探讨
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摘要
<正>药物化合物进入中枢神经系统(CNS)的两个主要障碍是血液-脑屏障(BBB)和血-脑脊液屏障(BCB)。考虑到毛细血管和神经元之间的最大距离小于8-20μm,BBB被认为对脑细胞外液发挥更大的控制作用~([1,2])。血-脑屏障(BBB)由内皮细胞和相邻的星形细胞、基底膜、周细胞和神经元组成。这些组成元素是功能性神经血管单位的一部分,其能提供输送必需的营养物质并排除潜在的有害分子进
引文
[1]Greenhalgh AD,Ogungbenro K,Rothwell NJ,et al.Translational pharmacokinetics:challenges of an emerging approach to drug development in stroke[J].Expert Opin Drug Metab Toxicol,2011,7(6):681-695.
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[6]Lochhead JJ,Thorne RG.Intranasal delivery of biologics to the central nervous system[J].Adv Drug Deliv Rev,2012,64(7):614-628.
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[8]William HFI.Method for administering neurologic agents to the brain:US 6180603 B1[P].2001-01-03.
[9]Dhuria SV,Hanson LR,Nd FW.Intranasal delivery to the central nervous system:mechanisms and experimental considerations[J].J Pharm Sci,2010,99(4):1654-1673.
[10]Thorne RG,Pronk GJ,Padmanabhan V,et al.Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration[J].Neuroscience,2004,127(2):481-496.
[11]Haspel JA,Choi AM.Approaches for drug deposition in the human olfactory epithelium[J].Pediatrics,2005,17(6):947-964.
[12]Gomez D,Martinez JA,Hanson LR,et al.Intranasal treatment of neurodegenerative diseases and stroke[J].Front Biosc,2012,4(1):74-89.
[13]Thorne RG,Hanson LR,Ross TM,et al.Delivery of interferonbeta to the monkey nervous system following intranasal administration[J].Neuroscience,2008,152(3):785-797.
[14]Hanson LR.Strategies for intranasal delivery of therapeutics for the prevention and treatment of neuroAIDS[J].J Neuroimmun Pharmacol,2007,2(1):81-86.
[15]Stuck BA.Smell and taste-the chemical senses[J].HNO,2010,58(7):643-651.
[16]Fuss SH,Omura M,Mombaerts P.The Grueneberg ganglion of the mouse projects axons to glomeruli in the olfactory bulb[J].Eur J Neurosci,2005,22(10):2649-2654.
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[20]Broadwell RD,Balin BJ.Endocytic and exocytic pathways of the neuronal secretory process and trans-synaptic transfer of wheat germ agglutinin-horseradish peroxidase in vivo[J].J Comp Neurol,1985,242(4):632-650.
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[24]Charlton ST,Whetstone J,Fayinka ST,et al.Evaluation of direct transport pathways of glycine receptor antagonists and an angiotensin antagonist from the nasal cavity to the central nervous system in the rat model[J].Pharmaceut Res,2008,25(7):1531-1543.
[25]Nonaka N,Farr SA,Kageyama H,et al.Delivery of galanin-like peptide to the brain:targeting with intranasal delivery and cyclodextrins[J].J Pharmacol Exp Ther,2008,325(2):513-519.
[26]Banks WA,During MJ,Niehoff ML.Brain uptake of the glucagon-like peptide-1 antagonist exendin(9-39)after intranasal administration[J].J Pharmacol Exp Ther,2004,309(2):469-476.
[27]Clerico DM,To WC,Lanza DC.Anatomy of the human nasal passages.[M].New York:Marcel Dekker,2003:1-16.
[28]Renner DB,Svitak AL,Gallus NJ,et al.Intranasal delivery of insulin via the olfactory nerve pathway[J].J Pharm Pharmacol,2012,64(12):1709-1714.
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[30]Thorne RG,Pronk GJ,Padmanabhan V,et al.Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration[J].Neuroscience,2004,127(2):481-496.
[31]Scranton RA,Fletcher L,Sprague S,et al.The rostral migratory stream plays a key role in intranasal delivery of drugs into the CNS[J].Plos One,2015,6(4):e18711.
[32]Thorne RG.Delivery of neurotrophic factors to the central nervous system:pharmacokinetic considerations[J].Clin Pharmacokinet,2001,40(12):907-946.
[33]Born J,Lange T,Kern W,et al.Sniffing neuropeptides:a transnasal approach to the human brain[J].Nat Neurosci,2002,5(6):514-516.
[34]Sorge NMV,Doran KS.Defense at the border:the blood-brain barrier versus bacterial foreigners[J].Future Microbiol,2012,7(3):383-394.
[35]Banks WA.Delivery of peptides to the brain:emphasis on therapeutic development[J].Peptide Sci,2008,90(5):589-594.
[36]Bitter C,Suter-Zimmermann K,Surber C.Nasal drug delivery in humans[J].Curr Probl Dermatol,2011,40(2):20-22.
[37]Lindup WE,Orme MC.Clinical pharmacology:plasma protein binding of drugs[J].BMJ,1981,282(6259):212-216.
[38]Jiang Y,Zhu J,Xu G,et al.Intranasal delivery of stem cells to the brain[J].Expert Opin Drug Deliv,2011,8(5):623-632.
[39]Frey WH,Liu J,Chen X,et al.Delivery of 125I-NGF to the brain via the olfactory route[J].Drug Deliv,1997,4(2):87-92.
[40]Dhuria SV,Hanson LR.Intranasal delivery to the central nervous system:mechanisms and experimental considerations[J].JPharm Sci,2010,99(4):1654-1673.
[41]Rodr2Guez-Frutos B,Otero-Ortega L,Guti2○C Rrez-Fern2n M,et al.Stem cell therapy and administration routes after stroke[J].Transl Stroke Res,2016,7(5):378-387.
[42]Sun BL,He MQ,Han XY,et al.Intranasal delivery of granulocyte colony-stimulating factor enhances its neuroprotective effects against ischemic brain injury in rats[J].Mol Neurobiol,2016,53(1):320-330.
[43]Zhu W,Cheng S,Xu G,et al.Intranasal nerve growth factor enhances striatal neurogenesis in adult rats with focal cerebral ischemia[J].Drug Deliv,2011,18(5):338-343.
[44]Garcia-Rodriguez JC,Sosa-Teste I.The nasal route as a potential pathway for delivery of erythropoietin in the treatment of acute ischemic stroke in humans[J].Sci World J,2009,9(3):970-981.
[45]Li J,Jie Y,Hui M,et al.Intranasal pretreatment with Z-ligustilide,the main volatile component of rhizoma chuanxiong,confers prophylaxis against cerebral ischemia via Nrf2 and HSP70 signaling pathways[J].J Agric Food Chem,2017,6(4):65-68.
[46]Ahmad N,Ahmad I,Umar S,et al.PNIPAM nanoparticles for targeted and enhanced nose-to-brain delivery of curcuminoids:UP-LC/ESI-Q-ToF-MS/MS-based pharmacokinetics and pharmacodynamic evaluation in cerebral ischemia model[J].Drug Deliv,2014,23(7):1-20.
[47]黄勇华,祝维峰.脑清喷鼻微乳治疗急性缺血性脑卒中的临床研究[J].中药材,2012,35(1):167-169.
[48]祝维峰,李丽霞,陈楚云,等.脑清喷鼻微乳对急性脑出血患者自由基水平及疗效的影响[J].山西中医学院学报,2015,16(1):34-36.
[49]陈颖,陈英梅,祝维峰,等.脑清喷鼻微乳含药血清对PC12细胞损伤模型的保护作用[J].中国中医基础医学杂志,2011,17(7):790-792.
[50]Illum L.Is nose-to-brain transport of drugs in man a reality?[J].J Pharm Pharmacol,2004,56(1):3-17.
[51]Kandimalla KK,Donovan MD.Localization and differential activity of P-glycoprotein in the bovine olfactory and nasal respiratory mucosae[J].Pharmaceut Res,2005,22(7):1121-1128.
[52]Graff CL,Pollack GM.Functional evidence for P-glycoprotein at the nose-brain barrier[J].Pharm Res,2005,22(1):86-93.
[53]Minn A,Leclerc S,Heydel JM,et al.Drug transport into the mammalian brain:the nasal pathway and its specific metabolic barrier[J].J Drug Target,2002,10(4):285-296.
[54]Chen SC,Eiting K,Cui K,et al.Therapeutic utility of a novel tight junction modulating peptide for enhancing intranasal drug delivery[J].J Pharm Sci,2006,95(6):1364-1371.
[55]Neuwelt E,Abbott NJ,Abrey L,et al.Strategies to advance translational research into brain barriers[J].Lancet Neurol,2008,7(1):84-96.
[56]Bruce WJ.Ultrastructure of human nasal mucosa[J].Laryngoscope,1983,93(12):1576-1599.
[2]Abbott N,Ronnback L,Hansson E.Astrocyte-endothelial interactions at the blood-brain barrier[J].Nat Rev Neurosci,2006,7(1):41-53.
[3]Abbott NJ,Patabendige AA,Dolman D E,et al.Structure and function of the blood-brain barrier[J].Neurobiol Dis,2010,37(1):13-25.
[4]Cecchelli R,Berezowski V,Lundquist S,et al.Modelling of the blood-brain barrier in drug discovery and development[J].Nat Rev Drug Discov,2007,6(8):650-661.
[5]Miller DS.Regulation of P-glycoprotein and other ABC drug transporters at the blood-brain barrier[J].Trends Pharmacol Sci,2010,31(6):246-254.
[6]Lochhead JJ,Thorne RG.Intranasal delivery of biologics to the central nervous system[J].Adv Drug Deliv Rev,2012,64(7):614-628.
[7]Kola I,Landis J.Can the pharmaceutical industry reduce attrition rates[J].Nat Rev Drug Discov,2004,3(8):711-715.
[8]William HFI.Method for administering neurologic agents to the brain:US 6180603 B1[P].2001-01-03.
[9]Dhuria SV,Hanson LR,Nd FW.Intranasal delivery to the central nervous system:mechanisms and experimental considerations[J].J Pharm Sci,2010,99(4):1654-1673.
[10]Thorne RG,Pronk GJ,Padmanabhan V,et al.Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration[J].Neuroscience,2004,127(2):481-496.
[11]Haspel JA,Choi AM.Approaches for drug deposition in the human olfactory epithelium[J].Pediatrics,2005,17(6):947-964.
[12]Gomez D,Martinez JA,Hanson LR,et al.Intranasal treatment of neurodegenerative diseases and stroke[J].Front Biosc,2012,4(1):74-89.
[13]Thorne RG,Hanson LR,Ross TM,et al.Delivery of interferonbeta to the monkey nervous system following intranasal administration[J].Neuroscience,2008,152(3):785-797.
[14]Hanson LR.Strategies for intranasal delivery of therapeutics for the prevention and treatment of neuroAIDS[J].J Neuroimmun Pharmacol,2007,2(1):81-86.
[15]Stuck BA.Smell and taste-the chemical senses[J].HNO,2010,58(7):643-651.
[16]Fuss SH,Omura M,Mombaerts P.The Grueneberg ganglion of the mouse projects axons to glomeruli in the olfactory bulb[J].Eur J Neurosci,2005,22(10):2649-2654.
[17]Balin BJ,Broadwell RD,Salcman M,et al.Avenues for entry of peripherally administered protein to the central nervous system in mouse,rat,and squirrel monkey[J].J Comp Neurol,1986,251(2):260-280.
[18]Jansson B,Bj9rk E.Visualization of in vivo olfactory uptake and transfer using fluorescein dextran[J].J Drug Target,2002,10(5):379-380.
[19]Ross TM,Zuckermann RN,Reinhard C.Intranasal administration delivers peptoids to the rat central nervous system[J].Neurosci Lett,2008,439(1):30-33.
[20]Broadwell RD,Balin BJ.Endocytic and exocytic pathways of the neuronal secretory process and trans-synaptic transfer of wheat germ agglutinin-horseradish peroxidase in vivo[J].J Comp Neurol,1985,242(4):632-650.
[21]Baker H,Spencer RF.Transneuronal transport of peroxidaseconjugated wheat germ agglutinin(WGA-HRP)from the olfactory epithelium to the brain of the adult rat[J].Exp Brain Res,1986,63(3):461-473.
[22]Thorne RG.Delivery of neurotrophic factors to the central nervous system:pharmacokinetic considerations[J].Clin Pharmacokinet,2001,40(12):907-946.
[23]Balin BJ,Broadwell RD,Salcman M,et al.Avenues for entry of peripherally administered protein to the central nervous system in mouse,rat,and squirrel monkey[J].J Comp Neurol,1986,251(2):260-280.
[24]Charlton ST,Whetstone J,Fayinka ST,et al.Evaluation of direct transport pathways of glycine receptor antagonists and an angiotensin antagonist from the nasal cavity to the central nervous system in the rat model[J].Pharmaceut Res,2008,25(7):1531-1543.
[25]Nonaka N,Farr SA,Kageyama H,et al.Delivery of galanin-like peptide to the brain:targeting with intranasal delivery and cyclodextrins[J].J Pharmacol Exp Ther,2008,325(2):513-519.
[26]Banks WA,During MJ,Niehoff ML.Brain uptake of the glucagon-like peptide-1 antagonist exendin(9-39)after intranasal administration[J].J Pharmacol Exp Ther,2004,309(2):469-476.
[27]Clerico DM,To WC,Lanza DC.Anatomy of the human nasal passages.[M].New York:Marcel Dekker,2003:1-16.
[28]Renner DB,Svitak AL,Gallus NJ,et al.Intranasal delivery of insulin via the olfactory nerve pathway[J].J Pharm Pharmacol,2012,64(12):1709-1714.
[29]Schaefer ML,B9ttger B,Silver WL,et al.Trigeminal collaterals in the nasal epithelium and olfactory bulb:a potential route for direct modulation of olfactory information by trigeminal stimuli[J].J Comp Neurol,2002,444(3):221-226.
[30]Thorne RG,Pronk GJ,Padmanabhan V,et al.Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration[J].Neuroscience,2004,127(2):481-496.
[31]Scranton RA,Fletcher L,Sprague S,et al.The rostral migratory stream plays a key role in intranasal delivery of drugs into the CNS[J].Plos One,2015,6(4):e18711.
[32]Thorne RG.Delivery of neurotrophic factors to the central nervous system:pharmacokinetic considerations[J].Clin Pharmacokinet,2001,40(12):907-946.
[33]Born J,Lange T,Kern W,et al.Sniffing neuropeptides:a transnasal approach to the human brain[J].Nat Neurosci,2002,5(6):514-516.
[34]Sorge NMV,Doran KS.Defense at the border:the blood-brain barrier versus bacterial foreigners[J].Future Microbiol,2012,7(3):383-394.
[35]Banks WA.Delivery of peptides to the brain:emphasis on therapeutic development[J].Peptide Sci,2008,90(5):589-594.
[36]Bitter C,Suter-Zimmermann K,Surber C.Nasal drug delivery in humans[J].Curr Probl Dermatol,2011,40(2):20-22.
[37]Lindup WE,Orme MC.Clinical pharmacology:plasma protein binding of drugs[J].BMJ,1981,282(6259):212-216.
[38]Jiang Y,Zhu J,Xu G,et al.Intranasal delivery of stem cells to the brain[J].Expert Opin Drug Deliv,2011,8(5):623-632.
[39]Frey WH,Liu J,Chen X,et al.Delivery of 125I-NGF to the brain via the olfactory route[J].Drug Deliv,1997,4(2):87-92.
[40]Dhuria SV,Hanson LR.Intranasal delivery to the central nervous system:mechanisms and experimental considerations[J].JPharm Sci,2010,99(4):1654-1673.
[41]Rodr2Guez-Frutos B,Otero-Ortega L,Guti2○C Rrez-Fern2n M,et al.Stem cell therapy and administration routes after stroke[J].Transl Stroke Res,2016,7(5):378-387.
[42]Sun BL,He MQ,Han XY,et al.Intranasal delivery of granulocyte colony-stimulating factor enhances its neuroprotective effects against ischemic brain injury in rats[J].Mol Neurobiol,2016,53(1):320-330.
[43]Zhu W,Cheng S,Xu G,et al.Intranasal nerve growth factor enhances striatal neurogenesis in adult rats with focal cerebral ischemia[J].Drug Deliv,2011,18(5):338-343.
[44]Garcia-Rodriguez JC,Sosa-Teste I.The nasal route as a potential pathway for delivery of erythropoietin in the treatment of acute ischemic stroke in humans[J].Sci World J,2009,9(3):970-981.
[45]Li J,Jie Y,Hui M,et al.Intranasal pretreatment with Z-ligustilide,the main volatile component of rhizoma chuanxiong,confers prophylaxis against cerebral ischemia via Nrf2 and HSP70 signaling pathways[J].J Agric Food Chem,2017,6(4):65-68.
[46]Ahmad N,Ahmad I,Umar S,et al.PNIPAM nanoparticles for targeted and enhanced nose-to-brain delivery of curcuminoids:UP-LC/ESI-Q-ToF-MS/MS-based pharmacokinetics and pharmacodynamic evaluation in cerebral ischemia model[J].Drug Deliv,2014,23(7):1-20.
[47]黄勇华,祝维峰.脑清喷鼻微乳治疗急性缺血性脑卒中的临床研究[J].中药材,2012,35(1):167-169.
[48]祝维峰,李丽霞,陈楚云,等.脑清喷鼻微乳对急性脑出血患者自由基水平及疗效的影响[J].山西中医学院学报,2015,16(1):34-36.
[49]陈颖,陈英梅,祝维峰,等.脑清喷鼻微乳含药血清对PC12细胞损伤模型的保护作用[J].中国中医基础医学杂志,2011,17(7):790-792.
[50]Illum L.Is nose-to-brain transport of drugs in man a reality?[J].J Pharm Pharmacol,2004,56(1):3-17.
[51]Kandimalla KK,Donovan MD.Localization and differential activity of P-glycoprotein in the bovine olfactory and nasal respiratory mucosae[J].Pharmaceut Res,2005,22(7):1121-1128.
[52]Graff CL,Pollack GM.Functional evidence for P-glycoprotein at the nose-brain barrier[J].Pharm Res,2005,22(1):86-93.
[53]Minn A,Leclerc S,Heydel JM,et al.Drug transport into the mammalian brain:the nasal pathway and its specific metabolic barrier[J].J Drug Target,2002,10(4):285-296.
[54]Chen SC,Eiting K,Cui K,et al.Therapeutic utility of a novel tight junction modulating peptide for enhancing intranasal drug delivery[J].J Pharm Sci,2006,95(6):1364-1371.
[55]Neuwelt E,Abbott NJ,Abrey L,et al.Strategies to advance translational research into brain barriers[J].Lancet Neurol,2008,7(1):84-96.
[56]Bruce WJ.Ultrastructure of human nasal mucosa[J].Laryngoscope,1983,93(12):1576-1599.