圆窗途径内耳药物载体的研究现状
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摘要
圆窗是内耳局部给药的重要途径,依托智能给药系统实现微创的内耳给药方法将具有很好的临床应用前景,而药物载体是构建智能给药系统的关键环节,目前在内耳局部药物研究中常用的载体有病毒载体、纳米粒载体、原位凝胶、蛋白质载体,本文重点介绍各类型载体在内耳局部给药系统研究应用的特点。
The round window is an important approach for delivering drugs into the inner ear. Intelligent delivery systems for minimally invasive inner ear drug administration show promising clinical application prospects. Drug carriers are the key to building an intelligent drug delivery system. Currently drug carriers that are commonly used in inner ear research include viral vectors, nanoparticle carriers, in situ gel and carrier proteins. This article focuses on the characteristics of various types of vehicles which have been applied in inner ear drug delivery systems.
The round window is an important approach for delivering drugs into the inner ear. Intelligent delivery systems for minimally invasive inner ear drug administration show promising clinical application prospects. Drug carriers are the key to building an intelligent drug delivery system. Currently drug carriers that are commonly used in inner ear research include viral vectors, nanoparticle carriers, in situ gel and carrier proteins. This article focuses on the characteristics of various types of vehicles which have been applied in inner ear drug delivery systems.
引文
1 Bowe SN.Round Window Perfusion Dynamics:Implications for IntracochlearTherapy[J].Current Opinion in Otolaryngology&Head and Neck Surgery,2010,18(5):377-385.
2 Chen G,Zhang X,Yang F.Disposition of Nanoparticle-Based Delivery System via Inner Ear Administration[J].Current Drug Metabolism,2010,11(10):886-897.
3 Shi X,Wu N,Zhang Y,et al.Adeno-Associated Virus Transformation into the Normal Miniature Pig and the Normal Guinea Pigs Cochlea via Scala Tympani[J].Acta Oto-Laryngologica,2017,137(9):910-916.
4 Derby ML,Sena-Esteves M,Breakefield XO.Gene Transfer into the Mammalian Inner Ear Using HSV-1 and Vaccinia Virus Vectors[J].Hearing Research,1999,134(1-2):1-8.
5 Xu H,Li Z.Nanocarriers in Gene Therapy:A Review[J].Journal o Biomedical Nanotechnology,2014,10(12):3483-3507.
6 Sacheli R,Delacroix L,Vandenackerveken P,et al.Gene Transfer in Inner Ear Cells:A Challenging Race[J].Gene Therapy,2013,20(3)237-247.
7 Shu Y,Tao Y,Li W,et al.Adenovirus Vectors Target Several Cel Subtypes of Mammalian Inner Ear In Vivo[J].Neural Plasticity2016;2016:9409846.
8 Staecker H,Li D,O'Malley BW.Gene Expression in the Mammalian Cochlea:A Study of Multiple Vector Systems[J].Acta Oto-Laryngologica,2001,121(2):157-163.
9 Suzuki M,Yamasoba T,Suzukawa K.Adenoviral Vector Gene Delivery via the Round Window Membrane in Guinea Pigs[J].Neuroreport,2003,14(15):1951-1955.
10 Luebke AE,Steiger JD,Hodges BL.A Modified Adenovirus Can Transfect Cochlear Hair Cells In Vivo without Compromising Cochlear Function[J].Gene Therapy,2001,8(10):789-794.
11 Jero J,Mhatre AN,Tseng CJ,et al.Cochlear Gene Delivery through an Intact Round Window Membrane in Mouse[J].Human Gene Therapy,2001,12(5):539-548.
12 Selot R,Arumugam S,Mary B,et al.Optimized AAV Rh10 Vectors That Partially Evade Neutralizing Antibodies during Hepatic Gene Transfer[J].Frontiers in Pharmacology,2017,8:441.
13 Luebke AE,Rova C,Von Doersten PG.Adenoviral and AAV-Mediated Gene Transfer to the Inner Ear:Role of Serotype,Promoter,and Viral Load on In Vivo and In Vitro Infection Efficiencies[J].Advances in Oto-Rhino-Laryngology,2009,66:87-98.
14 Liu Y,Okada T,Sheykholeslami K,et al.Specific and Efficient Transduction of Cochlear Inner Hair Cells with Recombinant Adeno-Associated Virus Type 3 Vector[J].Molecular Therapy:the Journal of the American Society of Gene Therapy,2005,12(4):725-733.
15 Bedrosian JC,Gratton MA,Brigande JV,et al.In Vivo Delivery of Recombinant Viruses to the Fetal Murine Cochlea:Transduction Characteristics and Long-Term Effects on Auditory Function[J].Molecular Therapy:the Journal of the American Society of Gene Therapy,2006,14(3):328-335.
16 Maass JC,Berndt FA,Cánovas J.P27Kip1 Knockdown Induces Proliferation in the Organ of Corti in Culture After Efficient ShRNALentiviral Transduction[J].Journal of the Association for Research in Otolaryngology:JARO,2013,14(4):495-508.
17 Pietola L,Aarnisalo AA,Joensuu J,et al.HOX-GFP and WOX-GFPLentivirus Vectors for Inner Ear Gene Transfer[J].Acta Oto-Laryngologica,2008,128(6):613-620.
18 Pan S,Wan J,Liu S,et al.Lentivirus Carrying the Atoh1 Gene Infects Normal Rat Cochlea[J].Neural Regeneration Research,2013,8(17):1551-1559.
19 Pyykk?I,Zou J,Zhang W.Nanoparticle-Based Delivery for the Treatment of Inner Ear Disorders[J].Current Opinion in Otolaryngology&Head and Neck Surgery,2011,19(5):388-396.
20陈文博.IL-10基因重组慢病毒载体不同途径导入内耳局部治疗自身免疫性感音神经性聋的实验研究[D].南京医科大学,2010.Chen WB.IL-10 Gene Recombinant Lentiviral Vector of Different Ways into the Inner Ear Local Treatment of Autoimmune Sensorineural Hearing Loss[D].Nanjing Medical University,2010.
21 Holt JR,Johns DC,Wang S,et al.Functional Expression of Exogenous Proteins in Mammalian Sensory Hair Cells Infected with Adenoviral Vectors[J].Journal of Neurophysiology,1999,81(4):1881-1888.
22 Mansfield DC,Kyula JN,Rosenfelder N,et al.Oncolytic Vaccinia Virus as a Vector for Therapeutic Sodium Iodide Symporter Gene Therapy in Prostate Cancer[J].Gene Therapy,2016,23(4):357-368.
23 Han JJ,Mhatre AN,Wareing M,et al.Transgene Expression in the Guinea Pig Cochlea Mediated by a Lentivirus-Derived Gene Transfer Vector[J].Human Gene Therapy,1999,10(11):1867-1873.
24 Geschwind MD,Hartnick CJ,Liu W,et al.Defective HSV-1 Vector Expressing BDNF in Auditory Ganglia Elicits Neurite Outgrowth:Model for Treatment of Neuron Loss Following Cochlear Degeneration[J].Human Gene Therapy,1996,7(2):173-182.
25 BuckiováD,Ranjan S,Newman TA,et al.Minimally Invasive Drug Delivery to the Cochlea through Application of Nanoparticles to the Round Window Membrane[J].Nanomedicine,2012,7(9):1339-1354.
26 Lajud SA,Nagda DA,Qiao P,et al.A Novel Chitosan-Hydrogel-Based Nanoparticle Delivery System for Local Inner Ear Application[J].Otolo Neurotol.2015,36(2):341-347.
27 Wareing M,Mhatre AN,Pettis R,et al.Cationic Liposome Mediated Transgene Expression in the Guinea Pig Cochlea[J].Hearing Research,1999,128(1-2):61-69.
28 Maeda Y,Fukushima K,Kawasaki A,et al.Cochlear Expression of a Dominant-Negative GJB2R75W Construct Delivered through the Round Window Membrane in Mice[J].Neuroscience Research2007,58(3):250-254.
29 Ge X,Jackson RL,Liu J,et al.Distribution of PLGA Nanoparticles in Chinchilla Cochleae[J].Otolaryngology--Head and Neck Surgery:Official Journal of American Academy of Otolaryngology-Head and Neck Surgery,2007,137(4):619-623.
30 Wen X,Ding S,Cai H,et al.Nanomedicine Strategy for Optimizing Delivery to Outer Hair Cells by Surface-Modified Poly(Lactic/Glycolic Acid)Nanoparticles with Hydrophilic Molecules[J].International Journal of Nanomedicine,2016,11:5959-5969.
31 Tamura T,Kita T,Nakagawa T,et al.Drug Delivery to the Cochlea Using PLGA Nanoparticles[J].The Laryngoscope,2005,115(11)2000-2005.
32 El Kechai N,Mamelle E,Nguyen Y,et al.Hyaluronic Acid Liposomal Gel Sustains Delivery of a Corticoid to the Inner Ear[J].J Control Release,2016,226:248-257.
33 Borden RC,Saunders JE,Berryhill WE,et al.Hyaluronic Acid Hydrogel Sustains the Delivery of Dexamethasone across the Round Window Membrane[J].Audiology&Neuro-Otology,2011,16(1):1-11.
34陈钢,张晓,卢刚等.鸦胆子油微囊-原位凝胶的制备及体外释药机制的研究[J].中草药,2012,43(07):1306-1309.Chen G,Zhang X,Lu G,et al.Preparation and In Vitro Release Mechanism of Brucea Javanica Oil Microencapsulated In Situ Gel[J].Chinese Traditional and Herbal Drugs,2012,43(07):1306-1309.
35 Endo T,Nakagawa T,Kita T,et al.Novel Strategy for Treatment of Inner Ears Using a Biodegradable Gel[J].The Laryngoscope,2005,115(11):2016-2020.
36 Qi W,Ding D,Zhu H,et al.Efficient SiRNA Transfection to the Inner Ear through the Intact Round Window by a Novel Proteidic Delivery Technology in the Chinchilla[J].Gene Therapy,2014,21(1):10-18.
2 Chen G,Zhang X,Yang F.Disposition of Nanoparticle-Based Delivery System via Inner Ear Administration[J].Current Drug Metabolism,2010,11(10):886-897.
3 Shi X,Wu N,Zhang Y,et al.Adeno-Associated Virus Transformation into the Normal Miniature Pig and the Normal Guinea Pigs Cochlea via Scala Tympani[J].Acta Oto-Laryngologica,2017,137(9):910-916.
4 Derby ML,Sena-Esteves M,Breakefield XO.Gene Transfer into the Mammalian Inner Ear Using HSV-1 and Vaccinia Virus Vectors[J].Hearing Research,1999,134(1-2):1-8.
5 Xu H,Li Z.Nanocarriers in Gene Therapy:A Review[J].Journal o Biomedical Nanotechnology,2014,10(12):3483-3507.
6 Sacheli R,Delacroix L,Vandenackerveken P,et al.Gene Transfer in Inner Ear Cells:A Challenging Race[J].Gene Therapy,2013,20(3)237-247.
7 Shu Y,Tao Y,Li W,et al.Adenovirus Vectors Target Several Cel Subtypes of Mammalian Inner Ear In Vivo[J].Neural Plasticity2016;2016:9409846.
8 Staecker H,Li D,O'Malley BW.Gene Expression in the Mammalian Cochlea:A Study of Multiple Vector Systems[J].Acta Oto-Laryngologica,2001,121(2):157-163.
9 Suzuki M,Yamasoba T,Suzukawa K.Adenoviral Vector Gene Delivery via the Round Window Membrane in Guinea Pigs[J].Neuroreport,2003,14(15):1951-1955.
10 Luebke AE,Steiger JD,Hodges BL.A Modified Adenovirus Can Transfect Cochlear Hair Cells In Vivo without Compromising Cochlear Function[J].Gene Therapy,2001,8(10):789-794.
11 Jero J,Mhatre AN,Tseng CJ,et al.Cochlear Gene Delivery through an Intact Round Window Membrane in Mouse[J].Human Gene Therapy,2001,12(5):539-548.
12 Selot R,Arumugam S,Mary B,et al.Optimized AAV Rh10 Vectors That Partially Evade Neutralizing Antibodies during Hepatic Gene Transfer[J].Frontiers in Pharmacology,2017,8:441.
13 Luebke AE,Rova C,Von Doersten PG.Adenoviral and AAV-Mediated Gene Transfer to the Inner Ear:Role of Serotype,Promoter,and Viral Load on In Vivo and In Vitro Infection Efficiencies[J].Advances in Oto-Rhino-Laryngology,2009,66:87-98.
14 Liu Y,Okada T,Sheykholeslami K,et al.Specific and Efficient Transduction of Cochlear Inner Hair Cells with Recombinant Adeno-Associated Virus Type 3 Vector[J].Molecular Therapy:the Journal of the American Society of Gene Therapy,2005,12(4):725-733.
15 Bedrosian JC,Gratton MA,Brigande JV,et al.In Vivo Delivery of Recombinant Viruses to the Fetal Murine Cochlea:Transduction Characteristics and Long-Term Effects on Auditory Function[J].Molecular Therapy:the Journal of the American Society of Gene Therapy,2006,14(3):328-335.
16 Maass JC,Berndt FA,Cánovas J.P27Kip1 Knockdown Induces Proliferation in the Organ of Corti in Culture After Efficient ShRNALentiviral Transduction[J].Journal of the Association for Research in Otolaryngology:JARO,2013,14(4):495-508.
17 Pietola L,Aarnisalo AA,Joensuu J,et al.HOX-GFP and WOX-GFPLentivirus Vectors for Inner Ear Gene Transfer[J].Acta Oto-Laryngologica,2008,128(6):613-620.
18 Pan S,Wan J,Liu S,et al.Lentivirus Carrying the Atoh1 Gene Infects Normal Rat Cochlea[J].Neural Regeneration Research,2013,8(17):1551-1559.
19 Pyykk?I,Zou J,Zhang W.Nanoparticle-Based Delivery for the Treatment of Inner Ear Disorders[J].Current Opinion in Otolaryngology&Head and Neck Surgery,2011,19(5):388-396.
20陈文博.IL-10基因重组慢病毒载体不同途径导入内耳局部治疗自身免疫性感音神经性聋的实验研究[D].南京医科大学,2010.Chen WB.IL-10 Gene Recombinant Lentiviral Vector of Different Ways into the Inner Ear Local Treatment of Autoimmune Sensorineural Hearing Loss[D].Nanjing Medical University,2010.
21 Holt JR,Johns DC,Wang S,et al.Functional Expression of Exogenous Proteins in Mammalian Sensory Hair Cells Infected with Adenoviral Vectors[J].Journal of Neurophysiology,1999,81(4):1881-1888.
22 Mansfield DC,Kyula JN,Rosenfelder N,et al.Oncolytic Vaccinia Virus as a Vector for Therapeutic Sodium Iodide Symporter Gene Therapy in Prostate Cancer[J].Gene Therapy,2016,23(4):357-368.
23 Han JJ,Mhatre AN,Wareing M,et al.Transgene Expression in the Guinea Pig Cochlea Mediated by a Lentivirus-Derived Gene Transfer Vector[J].Human Gene Therapy,1999,10(11):1867-1873.
24 Geschwind MD,Hartnick CJ,Liu W,et al.Defective HSV-1 Vector Expressing BDNF in Auditory Ganglia Elicits Neurite Outgrowth:Model for Treatment of Neuron Loss Following Cochlear Degeneration[J].Human Gene Therapy,1996,7(2):173-182.
25 BuckiováD,Ranjan S,Newman TA,et al.Minimally Invasive Drug Delivery to the Cochlea through Application of Nanoparticles to the Round Window Membrane[J].Nanomedicine,2012,7(9):1339-1354.
26 Lajud SA,Nagda DA,Qiao P,et al.A Novel Chitosan-Hydrogel-Based Nanoparticle Delivery System for Local Inner Ear Application[J].Otolo Neurotol.2015,36(2):341-347.
27 Wareing M,Mhatre AN,Pettis R,et al.Cationic Liposome Mediated Transgene Expression in the Guinea Pig Cochlea[J].Hearing Research,1999,128(1-2):61-69.
28 Maeda Y,Fukushima K,Kawasaki A,et al.Cochlear Expression of a Dominant-Negative GJB2R75W Construct Delivered through the Round Window Membrane in Mice[J].Neuroscience Research2007,58(3):250-254.
29 Ge X,Jackson RL,Liu J,et al.Distribution of PLGA Nanoparticles in Chinchilla Cochleae[J].Otolaryngology--Head and Neck Surgery:Official Journal of American Academy of Otolaryngology-Head and Neck Surgery,2007,137(4):619-623.
30 Wen X,Ding S,Cai H,et al.Nanomedicine Strategy for Optimizing Delivery to Outer Hair Cells by Surface-Modified Poly(Lactic/Glycolic Acid)Nanoparticles with Hydrophilic Molecules[J].International Journal of Nanomedicine,2016,11:5959-5969.
31 Tamura T,Kita T,Nakagawa T,et al.Drug Delivery to the Cochlea Using PLGA Nanoparticles[J].The Laryngoscope,2005,115(11)2000-2005.
32 El Kechai N,Mamelle E,Nguyen Y,et al.Hyaluronic Acid Liposomal Gel Sustains Delivery of a Corticoid to the Inner Ear[J].J Control Release,2016,226:248-257.
33 Borden RC,Saunders JE,Berryhill WE,et al.Hyaluronic Acid Hydrogel Sustains the Delivery of Dexamethasone across the Round Window Membrane[J].Audiology&Neuro-Otology,2011,16(1):1-11.
34陈钢,张晓,卢刚等.鸦胆子油微囊-原位凝胶的制备及体外释药机制的研究[J].中草药,2012,43(07):1306-1309.Chen G,Zhang X,Lu G,et al.Preparation and In Vitro Release Mechanism of Brucea Javanica Oil Microencapsulated In Situ Gel[J].Chinese Traditional and Herbal Drugs,2012,43(07):1306-1309.
35 Endo T,Nakagawa T,Kita T,et al.Novel Strategy for Treatment of Inner Ears Using a Biodegradable Gel[J].The Laryngoscope,2005,115(11):2016-2020.
36 Qi W,Ding D,Zhu H,et al.Efficient SiRNA Transfection to the Inner Ear through the Intact Round Window by a Novel Proteidic Delivery Technology in the Chinchilla[J].Gene Therapy,2014,21(1):10-18.