Show simple item record

dc.contributor.advisorEROĞLU, Hakan
dc.contributor.authorHAİDAR, Mohammad Karim
dc.date.accessioned2018-11-13T11:19:03Z
dc.date.issued2018-11-13
dc.date.submitted2018-10-22
dc.identifier.citation1. Grinsell D, Keating CP. Peripheral nerve reconstruction after injury: a review of clinical and experimental therapies. Biomed Res Int. 2014;2014:698256. 2. López-Cebral R, Silva-Correia J, Reis RL, Silva TH, Oliveira JM. Peripheral Nerve Injury: Current Challenges, Conventional Treatment Approaches, and New Trends in Biomaterials-Based Regenerative Strategies. ACS Biomaterials Science & Engineering. 2017;3(12):3098-122. 3. Kehoe S, Zhang XF, Boyd D. FDA approved guidance conduits and wraps for peripheral nerve injury: a review of materials and efficacy. Injury. 2012;43(5):553-72. 4. Belkas JS, Shoichet MS, Midha R. Axonal guidance channels in peripheral nerve regeneration. Operative techniques in Orthopaedics. 2004;14(3):190-8. 5. Noback CR, Strominger NL, Demarest RJ, Ruggiero DA. The human nervous system: structure and function. Totowa, New Jersey: Springer Science & Business Media; 2005. 6. Premkumar K. The massage connection: anatomy and physiology: Lippincott Williams & Wilkins; 2004. 7. Goodman AA, Dunton T. Understanding the Human Body: An Introduction to Anatomy and Physiology: teaching Company; 2004. 8. Evans-Martin FF. The nervous system. New York: Chelsea House; 2010. 222 p. p. 9. Treuting PM, Dintzis SM, Liggitt D, Frevert CW. Comparative anatomy and histology: a mouse and human atlas (expert consult): Academic Press; 2011. 10. Tortora GJ, Grabowski SR. Introduction to the human body: Harper & Row; 1988. 11. Brodal P. The central nervous system: structure and function: Oxford University Press; 2004. 12. Lundy-Ekman L. Neuroscience-E-Book: Fundamentals for Rehabilitation: Elsevier Health Sciences; 2013. 13. Neuron Shape Classification.jpg - Wikimedia Commons [Internet]. Commons.wikimedia.org. 2018 [cited 12 February 2018]. Available from: https://commons.wikimedia.org/wiki/File:1207_Neuron_Shape_Classification.jpg. 14. Snell RS. Clinical neuroanatomy: Lippincott Williams & Wilkins; 2010. 15. Betts JG, College O, Desaix P, Johnson JE, Johnson EW, Korol O, et al. Anatomy and Physiology: OpenStax College; 2013. 16. Maccaferri G, Lacaille J-C. Interneuron Diversity series: Hippocampal interneuron classifications–making things as simple as possible, not simpler. Trends in neurosciences. 2003;26(10):564-71. 17. Neurons and Glial Cells | Boundless Biology [Internet]. Courses.lumenlearning.com. 2018 [cited 16 April 2018]. Available from: https://courses.lumenlearning.com/boundless-biology/chapter/neurons-and-glial-cells/ 18. Verkhratskiĭ AN, Butt A. Glial neurobiology : a textbook. Chichester, England a; Hoboken, NJ: John Wiley & Sons; 2007. xiv, 215 p. p. 19. Pfaff DW, Volkow ND. Neuroscience in the 21st century: from basic to clinical. q, editor: Springer; 2016. 20. The Peripheral Nervous System · Anatomy and Physiology [Internet]. Philschatz.com. 2018 [cited 16 April 2018]. Available from: http://philschatz.com/anatomy-book/contents/m46553.html 21. Barral JP, Croibier A. Manual therapy for the peripheral nerves. Edinburgh ; New York: Churchill Livingstone/Elsevier; 2007. xviii, 270 p. p. 22. Barral J-P, Croibier A. Chapter 1 - Some preliminary thoughts. Manual Therapy for the Cranial Nerves. Edinburgh: Churchill Livingstone; 2009. p. 1-5. 23. Peltonen S, Alanne M, Peltonen J. Barriers of the peripheral nerve. Tissue Barriers. 2013;1(3):e24956. 24. Stewart JD. Peripheral nerve fascicles: anatomy and clinical relevance. Muscle Nerve. 2003;28(5):525-41. 25. Bhatheja K, Field J. Schwann cells: origins and role in axonal maintenance and regeneration. Int J Biochem Cell Biol. 2006;38(12):1995-9. 26. Saher G, Brugger B, Lappe-Siefke C, Mobius W, Tozawa R, Wehr MC, et al. High cholesterol level is essential for myelin membrane growth. Nature neuroscience. 2005;8(4):468-75. 27. Said G, Krarup C. Peripheral nerve disorders. Edinburgh: Elsevier; 2013. xx, 987 pages p. 28. Garbay B, Heape AM, Sargueil F, Cassagne C. Myelin synthesis in the peripheral nervous system. Prog Neurobiol. 2000;61(3):267-304. 29. Rigoard P. Atlas of Anatomy of the Peripheral Nerves: The Nerves of the Limbs–Student Edition: Springer; 2017. 30. Brown AG. Nerve cells and nervous systems: an introduction to neuroscience: Springer Science & Business Media; 2012. 31. Nebylitsyn V. Fundamental properties of the human nervous system: Springer Science & Business Media; 2013. 32. Fain GL, O'Dell T. Molecular and cellular physiology of neurons. Second edition. ed. Cambridge, Massachusetts: Harvard University Press; 2014. xi, 735 pages p. 33. Repair, protection and regeneration of peripheral nerve injury. Neural Regen Res. 2015;10(11):1777-98. 34. Latov N. Peripheral neuropathy : when the numbness, weakness, and pain won't stop. New York Saint Paul, MN: Demos ; AAN Press : Distributed to the trade by Publishers Group West; 2007. xiii, 134 p. p. 35. Eroğlu H, Haidar MK, Nemutlu E, Öztürk Ş, Bayram C, Ulubayram K, et al. Dual release behavior of atorvastatin and alpha-lipoic acid from PLGA microspheres for the combination therapy in peripheral nerve injury. Journal of Drug Delivery Science and Technology. 2017;39:455-66. 36. Rodríguez FJ, Valero-Cabré A, Navarro X. Regeneration and functional recovery following peripheral nerve injury. Drug Discovery Today: Disease Models. 2004;1(2):177-85. 37. Rubin DI, Hermann RC. CHAPTER 105 - PERIPHERAL NERVE INJURY A2 - Schapira, Anthony H.V. In: Editors A, Byrne E, DiMauro S, Frackowiak RSJ, Johnson RT, Mizuno Y, et al., editors. Neurology and Clinical Neuroscience. Philadelphia: Mosby; 2007. p. 1409-22. 38. Ditty BJ, Omar NB, Rozzelle CJ. Chapter 24 - Surgery for Peripheral Nerve Trauma A2 - Tubbs, R. Shane. In: Rizk E, Shoja MM, Loukas M, Barbaro N, Spinner RJ, editors. Nerves and Nerve Injuries. San Diego: Academic Press; 2015. p. 373-81. 39. Timothy H. Nerve injury: Classification, clinical assessment, investigation, and management. Handchirurgie Weltweit eV, editor Living Textbook of Hand Surgery. Cologne: gms; 2014. 40. Chhabra A, Ahlawat S, Belzberg A, Andreseik G. Peripheral nerve injury grading simplified on MR neurography: As referenced to Seddon and Sunderland classifications. The Indian Journal of Radiology & Imaging. 2014;24(3):217-24. 41. Hall S. The response to injury in the peripheral nervous system. The Journal of bone and joint surgery British volume. 2005;87(10):1309-19. 42. Neukomm LJ, Freeman MR. Diverse cellular and molecular modes of axon degeneration. Trends in cell biology. 2014;24(9):515-23. 43. Glass JD, Culver DG, Levey AI, Nash NR. Very early activation of m-calpain in peripheral nerve during Wallerian degeneration. Journal of the neurological sciences. 2002;196(1):9-20. 44. Coleman M. Axon degeneration mechanisms: commonality amid diversity. Nature Reviews Neuroscience. 2005;6(11):889. 45. Beirowski B, Adalbert R, Wagner D, Grumme DS, Addicks K, Ribchester RR, et al. The progressive nature of Wallerian degeneration in wild-type and slow Wallerian degeneration (Wld S) nerves. BMC neuroscience. 2005;6(1):6. 46. Fernandez-Valle C, Bunge RP, Bunge MB. Schwann cells degrade myelin and proliferate in the absence of macrophages: evidence fromin vitro studies of Wallerian degeneration. Journal of neurocytology. 1995;24(9):667-79. 47. Yan T, Feng Y, Zhai Q. Axon degeneration: Mechanisms and implications of a distinct program from cell death. Neurochem Int. 2010;56(4):529-34. 48. Pellegrino R, Politis M, Ritchie J, Spencer P. Events in degenerating cat peripheral nerve: induction of Schwann cell S phase and its relation to nerve fibre degeneration. Journal of neurocytology. 1986;15(1):17-28. 49. Scheib J, Höke A. Advances in peripheral nerve regeneration. Nature Reviews Neurology. 2013;9(12):668. 50. Stoll G, Griffin J, Li CY, Trapp B. Wallerian degeneration in the peripheral nervous system: participation of both Schwann cells and macrophages in myelin degradation. Journal of neurocytology. 1989;18(5):671-83. 51. Baichwal R, Bigbee J, DeVries G. Macrophage-mediated myelin-related mitogenic factor for cultured Schwann cells. Proceedings of the National Academy of Sciences. 1988;85(5):1701-5. 52. Dieu T, Johnstone BR, Newgreen DF. Genes and nerves. Journal of reconstructive microsurgery. 2005;21(3):179-86. 53. Stoll G, Muller HW. Nerve injury, axonal degeneration and neural regeneration: basic insights. Brain Pathol. 1999;9(2):313-25. 54. Dubovy P. Wallerian degeneration and peripheral nerve conditions for both axonal regeneration and neuropathic pain induction. Ann Anat. 2011;193(4):267-75. 55. Salgado C, Vilson F, Miller NR, Bernstein SL. Cellular inflammation in nonarteritic anterior ischemic optic neuropathy and its primate model. Archives of ophthalmology (Chicago, Ill : 1960). 2011;129(12):1583-91. 56. Fregnan F, Muratori L, Simões AR, Giacobini-Robecchi MG, Raimondo S. Role of inflammatory cytokines in peripheral nerve injury. Neural regeneration research. 2012;7(29):2259. 57. Shamash S, Reichert F, Rotshenker S. The cytokine network of Wallerian degeneration: tumor necrosis factor-α, interleukin-1α, and interleukin-1β. Journal of Neuroscience. 2002;22(8):3052-60. 58. Rotshenker S. Wallerian degeneration: the innate-immune response to traumatic nerve injury. Journal of neuroinflammation. 2011;8:109. 59. Ide C. Peripheral nerve regeneration. Neuroscience research. 1996;25(2):101-21. 60. Mietto BS, Mostacada K, Martinez AMB. Neurotrauma and inflammation: CNS and PNS responses. Mediators of inflammation. 2015;2015. 61. Navarro X, Vivó M, Valero-Cabré A. Neural plasticity after peripheral nerve injury and regeneration. Progress in neurobiology. 2007;82(4):163-201. 62. Sahni V, Qi Y, Frostick S. Peripheral nerve regeneration. European Surgery. 2005;37(4):187-92. 63. Burnett MG, Zager EL. Pathophysiology of peripheral nerve injury: a brief review. Neurosurg Focus. 2004;16(5):E1. 64. Campbell WW. Evaluation and management of peripheral nerve injury. Clinical neurophysiology. 2008;119(9):1951-65. 65. Menorca RM, Fussell TS, Elfar JC. Peripheral nerve trauma: mechanisms of injury and recovery. Hand clinics. 2013;29(3):317. 66. Menorca RMG, Fussell TS, Elfar JC. Nerve Physiology: Mechanisms of Injury and Recovery. Hand Clinics. 2013;29(3):317-30. 67. Christie K, Zochodne D. Peripheral axon regrowth: new molecular approaches. Neuroscience. 2013;240:310-24. 68. Allodi I, Udina E, Navarro X. Specificity of peripheral nerve regeneration: interactions at the axon level. Progress in neurobiology. 2012;98(1):16-37. 69. Wen Z, Zheng JQ. Directional guidance of nerve growth cones. Current Opinion in Neurobiology. 2006;16(1):52-8. 70. Dickson BJ. Molecular Mechanisms of Axon Guidance. Science. 2002;298(5600):1959-64. 71. M.F G, M M, S H, Khan WS. Peripheral Nerve Injury: Principles for Repair and Regeneration. The Open Orthopaedics Journal. 2014;8:199-203. 72. Zhang L, Webster TJ. Nanotechnology and nanomaterials: promises for improved tissue regeneration. Nano today. 2009;4(1):66-80. 73. Andrady AL. Science and technology of polymer nanofibers: John Wiley & Sons; 2008. 74. MacDiarmid A, Jones W, Norris I, Gao J, Johnson A, Pinto N, et al. Electrostatically-generated nanofibers of electronic polymers. Synthetic Metals. 2001;119(1-3):27-30. 75. Rošic R, Kocbek P, Pelipenko J, Kristl J, Baumgartner S. Nanofibers and their biomedical use. Acta pharmaceutica. 2013;63(3):295-304. 76. Gonsalves K, Halberstadt C, Laurencin CT, Nair L. Biomedical nanostructures: John Wiley & Sons; 2007. 77. Wei Q. Functional nanofibers and their applications: Elsevier; 2012. 78. Kowalczyk T, Nowicka A, Elbaum D, Kowalewski TA. Electrospinning of bovine serum albumin. Optimization and the use for production of biosensors. Biomacromolecules. 2008;9(7):2087-90. 79. Dzenis Y. Spinning continuous fibers for nanotechnology. Science. 2004;304(5679):1917-9. 80. Haghi A. Electrospinning of Nanofibers in Textiles: CRC Press; 2011. 81. Ramakrishna S. An introduction to electrospinning and nanofibers: World Scientific; 2005. 82. He C, Nie W, Feng W. Engineering of biomimetic nanofibrous matrices for drug delivery and tissue engineering. Journal of Materials Chemistry B. 2014;2(45):7828-48. 83. Morie A, Garg T, Goyal AK, Rath G. Nanofibers as novel drug carrier–an overview. Artificial cells, nanomedicine, and biotechnology. 2016;44(1):135-43. 84. Greiner A, Wendorff JH. Electrospinning: a fascinating method for the preparation of ultrathin fibers. Angewandte Chemie International Edition. 2007;46(30):5670-703. 85. Li D, Xia Y. Electrospinning of nanofibers: reinventing the wheel? Advanced materials. 2004;16(14):1151-70. 86. Haidar MK, Eroglu H. Nanofibers: New Insights for Drug Delivery and Tissue Engineering. Current topics in medicinal chemistry. 2017;17(13):1564-79. 87. Sill TJ, von Recum HA. Electrospinning: applications in drug delivery and tissue engineering. Biomaterials. 2008;29(13):1989-2006. 88. Inai R, Kotaki M, Ramakrishna S. Structure and properties of electrospun PLLA single nanofibres. Nanotechnology. 2005;16(2):208. 89. Katti DS, Robinson KW, Ko FK, Laurencin CT. Bioresorbable nanofiber‐based systems for wound healing and drug delivery: Optimization of fabrication parameters. Journal of Biomedical Materials Research Part B: Applied Biomaterials. 2004;70(2):286-96. 90. Son WK, Youk JH, Lee TS, Park WH. The effects of solution properties and polyelectrolyte on electrospinning of ultrafine poly (ethylene oxide) fibers. polymer. 2004;45(9):2959-66. 91. Fong H, Chun I, Reneker D. Beaded nanofibers formed during electrospinning. Polymer. 1999;40(16):4585-92. 92. Liu F, Guo R, Shen M, Wang S, Shi X. Effect of processing variables on the morphology of electrospun poly [(lactic acid)‐co‐(glycolic acid)] nanofibers. Macromolecular materials and engineering. 2009;294(10):666-72. 93. Megelski S, Stephens JS, Chase DB, Rabolt JF. Micro-and nanostructured surface morphology on electrospun polymer fibers. Macromolecules. 2002;35(22):8456-66. 94. De Vrieze S, Van Camp T, Nelvig A, Hagström B, Westbroek P, De Clerck K. The effect of temperature and humidity on electrospinning. Journal of materials science. 2009;44(5):1357. 95. Hardick O, Stevens B, Bracewell DG. Nanofibre fabrication in a temperature and humidity controlled environment for improved fibre consistency. Journal of materials science. 2011;46(11):3890-8. 96. Ramakrishna S. An introduction to electrospinning and nanofibers. Hackensack, NJ: World Scientific; 2005. xi, 382 p. p. 97. Huang Z-M, Zhang Y-Z, Kotaki M, Ramakrishna S. A review on polymer nanofibers by electrospinning and their applications in nanocomposites. Composites science and technology. 2003;63(15):2223-53. 98. Mauck RL, Baker BM, Nerurkar NL, Burdick JA, Li WJ, Tuan RS, et al. Engineering on the straight and narrow: the mechanics of nanofibrous assemblies for fiber-reinforced tissue regeneration. Tissue engineering Part B, Reviews. 2009;15(2):171-93. 99. Li WJ, Cooper JA, Jr., Mauck RL, Tuan RS. Fabrication and characterization of six electrospun poly(alpha-hydroxy ester)-based fibrous scaffolds for tissue engineering applications. Acta biomaterialia. 2006;2(4):377-85. 100. Chew SY, Hufnagel TC, Lim CT, Leong KW. Mechanical properties of single electrospun drug-encapsulated nanofibres. Nanotechnology. 2006;17(15):3880. 101. Moffat KL, Kwei AS-P, Spalazzi JP, Doty SB, Levine WN, Lu HH. Novel nanofiber-based scaffold for rotator cuff repair and augmentation. Tissue Engineering Part A. 2008;15(1):115-26. 102. Pietrzak WS, Sarver DR, Verstynen ML. Bioabsorbable polymer science for the practicing surgeon. The Journal of craniofacial surgery. 1997;8(2):87-91. 103. Therin M, Christel P, Li S, Garreau H, Vert M. In vivo degradation of massive poly (α-hydroxy acids): validation of in vitro findings. Biomaterials. 1992;13(9):594-600. 104. Liu W, Thomopoulos S, Xia Y. Electrospun nanofibers for regenerative medicine. Advanced healthcare materials. 2012;1(1):10-25. 105. Bölgen N, Vargel I, Korkusuz P, Menceloğlu YZ, Pişkin E. In vivo performance of antibiotic embedded electrospun PCL membranes for prevention of abdominal adhesions. Journal of Biomedical Materials Research Part B: Applied Biomaterials. 2007;81(2):530-43. 106. Monteiro N, Martins M, Martins A, Fonseca NA, Moreira JN, Reis RL, et al. Antibacterial activity of chitosan nanofiber meshes with liposomes immobilized releasing gentamicin. Acta biomaterialia. 2015;18:196-205. 107. Liu S, Zhou G, Liu D, Xie Z, Huang Y, Wang X, et al. Inhibition of orthotopic secondary hepatic carcinoma in mice by doxorubicin-loaded electrospun polylactide nanofibers. Journal of Materials Chemistry B. 2013;1(1):101-9. 108. Tian L, Prabhakaran MP, Hu J, Chen M, Besenbacher F, Ramakrishna S. Coaxial electrospun poly (lactic acid)/silk fibroin nanofibers incorporated with nerve growth factor support the differentiation of neuronal stem cells. RSC Advances. 2015;5(62):49838-48. 109. Xu X, Yang L, Xu X, Wang X, Chen X, Liang Q, et al. Ultrafine medicated fibers electrospun from W/O emulsions. Journal of Controlled Release. 2005;108(1):33-42. 110. Zamani M, Prabhakaran MP, Ramakrishna S. Advances in drug delivery via electrospun and electrosprayed nanomaterials. International journal of nanomedicine. 2013;8:2997. 111. Son YJ, Kim WJ, Yoo HS. Therapeutic applications of electrospun nanofibers for drug delivery systems. Archives of pharmacal research. 2014;37(1):69-78. 112. Zeng J, Yang L, Liang Q, Zhang X, Guan H, Xu X, et al. Influence of the drug compatibility with polymer solution on the release kinetics of electrospun fiber formulation. Journal of controlled release. 2005;105(1-2):43-51. 113. Zeng J, Aigner A, Czubayko F, Kissel T, Wendorff JH, Greiner A. Poly (vinyl alcohol) nanofibers by electrospinning as a protein delivery system and the retardation of enzyme release by additional polymer coatings. Biomacromolecules. 2005;6(3):1484-8. 114. Zhang J-F, Yang D-Z, Xu F, Zhang Z-P, Yin R-X, Nie J. Electrospun core− shell structure nanofibers from homogeneous solution of poly (ethylene oxide)/chitosan. Macromolecules. 2009;42(14):5278-84. 115. Gupta P, Wilkes GL. Some investigations on the fiber formation by utilizing a side-by-side bicomponent electrospinning approach. Polymer. 2003;44(20):6353-9. 116. Moghe A, Gupta B. Co‐axial electrospinning for nanofiber structures: preparation and applications. Polymer Reviews. 2008;48(2):353-77. 117. Jiang H, Wang L, Zhu K. Coaxial electrospinning for encapsulation and controlled release of fragile water-soluble bioactive agents. Journal of Controlled Release. 2014;193:296-303. 118. Wang X, Yuan Y, Huang X, Yue T. Controlled release of protein from core–shell nanofibers prepared by emulsion electrospinning based on green chemical. Journal of Applied Polymer Science. 2015;132(16). 119. Bazilevsky AV, Yarin AL, Megaridis CM. Co-electrospinning of core− shell fibers using a single-nozzle technique. Langmuir. 2007;23(5):2311-4. 120. Theron A, Zussman E, Yarin A. Electrostatic field-assisted alignment of electrospun nanofibres. Nanotechnology. 2001;12(3):384. 121. Pillay V, Dott C, Choonara YE, Tyagi C, Tomar L, Kumar P, et al. A review of the effect of processing variables on the fabrication of electrospun nanofibers for drug delivery applications. Journal of Nanomaterials. 2013;2013. 122. Fu Y, Kao WJ. Drug release kinetics and transport mechanisms of non-degradable and degradable polymeric delivery systems. Expert opinion on drug delivery. 2010;7(4):429-44. 123. Fang J, Niu H, Lin T, Wang X. Applications of electrospun nanofibers. Chinese Science Bulletin. 2008;53(15):2265. 124. Vester H, Wildemann B, Schmidmaier G, Stockle U, Lucke M. Gentamycin delivered from a PDLLA coating of metallic implants: In vivo and in vitro characterisation for local prophylaxis of implant-related osteomyelitis. Injury. 2010;41(10):1053-9. 125. Del Pozo JL, Patel R. Clinical practice. Infection associated with prosthetic joints. The New England journal of medicine. 2009;361(8):787-94. 126. Zhang L, Yan J, Yin Z, Tang C, Guo Y, Li D, et al. Electrospun vancomycin-loaded coating on titanium implants for the prevention of implant-associated infections. International journal of nanomedicine. 2014;9:3027. 127. Liu K-S, Lee C-H, Wang Y-C, Liu S-J. Sustained release of vancomycin from novel biodegradable nanofiber-loaded vascular prosthetic grafts: in vitro and in vivo study. International journal of nanomedicine. 2015;10:885. 128. Khil MS, Cha DI, Kim HY, Kim IS, Bhattarai N. Electrospun nanofibrous polyurethane membrane as wound dressing. Journal of Biomedical Materials Research Part B: Applied Biomaterials. 2003;67(2):675-9. 129. Jannesari M, Varshosaz J, Morshed M, Zamani M. Composite poly (vinyl alcohol)/poly (vinyl acetate) electrospun nanofibrous mats as a novel wound dressing matrix for controlled release of drugs. International journal of nanomedicine. 2011;6:993. 130. He T, Wang J, Huang P, Zeng B, Li H, Cao Q, et al. Electrospinning polyvinylidene fluoride fibrous membranes containing anti-bacterial drugs used as wound dressing. Colloids and Surfaces B: Biointerfaces. 2015;130:278-86. 131. Nitanan T, Akkaramongkolporn P, Rojanarata T, Ngawhirunpat T, Opanasopit P. Neomycin-loaded poly (styrene sulfonic acid-co-maleic acid)(PSSA-MA)/polyvinyl alcohol (PVA) ion exchange nanofibers for wound dressing materials. International journal of pharmaceutics. 2013;448(1):71-8. 132. Unnithan AR, Gnanasekaran G, Sathishkumar Y, Lee YS, Kim CS. Electrospun antibacterial polyurethane–cellulose acetate–zein composite mats for wound dressing. Carbohydrate polymers. 2014;102:884-92. 133. Liao N, Unnithan AR, Joshi MK, Tiwari AP, Hong ST, Park C-H, et al. Electrospun bioactive poly (ɛ-caprolactone)–cellulose acetate–dextran antibacterial composite mats for wound dressing applications. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2015;469:194-201. 134. Zhao R, Li X, Sun B, Tong Y, Jiang Z, Wang C. Nitrofurazone-loaded electrospun PLLA/sericin-based dual-layer fiber mats for wound dressing applications. RSC Advances. 2015;5(22):16940-9. 135. Xu X, Chen X, Xu X, Lu T, Wang X, Yang L, et al. BCNU-loaded PEG–PLLA ultrafine fibers and their in vitro antitumor activity against Glioma C6 cells. Journal of Controlled Release. 2006;114(3):307-16. 136. Wang Y, Wang B, Qiao W, Yin T. A novel controlled release drug delivery system for multiple drugs based on electrospun nanofibers containing nanoparticles. Journal of pharmaceutical sciences. 2010;99(12):4805-11. 137. Luo X, Zhang H, Chen M, Wei J, Zhang Y, Li X. Antimetastasis and antitumor efficacy promoted by sequential release of vascular disrupting and chemotherapeutic agents from electrospun fibers. International journal of pharmaceutics. 2014;475(1-2):438-49. 138. Crucho CI, Barros MT. Polymeric nanoparticles: A study on the preparation variables and characterization methods. Materials Science and Engineering: C. 2017;80:771-84. 139. Nagavarma B, Yadav HK, Ayaz A, Vasudha L, Shivakumar H. Different techniques for preparation of polymeric nanoparticles-a review. Asian J Pharm Clin Res. 2012;5(3):16-23. 140. Banik BL, Fattahi P, Brown JL. Polymeric nanoparticles: the future of nanomedicine. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology. 2016;8(2):271-99. 141. Pal SL, Jana U, Manna PK, Mohanta GP, Manavalan R. Nanoparticle: An overview of preparation and characterization (2000-2010). 2011. 142. Mohanty B, Aswal V, Kohlbrecher J, Bohidar H. Synthesis of gelatin nanoparticles via simple coacervation. Journal of Surface Science and Technology. 2005;21(3/4):149. 143. Langer K, Balthasar S, Vogel V, Dinauer N, von Briesen H, Schubert D. Optimization of the preparation process for human serum albumin (HSA) nanoparticles. International Journal of Pharmaceutics. 2003;257(1):169-80. 144. Agnihotri SA, Mallikarjuna NN, Aminabhavi TM. Recent advances on chitosan-based micro-and nanoparticles in drug delivery. Journal of controlled release. 2004;100(1):5-28. 145. Kunjachan S, Jose S, Lammers T. Understanding the mechanism of ionic gelation for synthesis of chitosan nanoparticles using qualitative techniques. Asian Journal of Pharmaceutics (AJP): Free full text articles from Asian J Pharm. 2014;4(2). 146. Calvo P, Remuñán-López C, Vila-Jato JL, Alonso MJ. Novel hydrophilic chitosan-polyethylene oxide nanoparticles as protein carriers. Journal of Applied Polymer Science. 1997;63(1):125-32. 147. Allouche J. Synthesis of organic and bioorganic nanoparticles: an overview of the preparation methods. Nanomaterials: A Danger or a Promise?: Springer; 2013. p. 27-74. 148. Ahlin Grabnar P, Kristl J. The manufacturing techniques of drug-loaded polymeric nanoparticles from preformed polymers. Journal of microencapsulation. 2011;28(4):323-35. 149. Tewes F, Munnier E, Antoon B, Ngaboni Okassa L, Cohen-Jonathan S, Marchais H, et al. Comparative study of doxorubicin-loaded poly(lactide-co-glycolide) nanoparticles prepared by single and double emulsion methods. European Journal of Pharmaceutics and Biopharmaceutics. 2007;66(3):488-92. 150. Pandey A, Pandey G. Research and Reviews: Journal of Pharmaceutics and Nanotechnology. 2015. 151. Lee SH, Heng D, Ng WK, Chan H-K, Tan RB. Nano spray drying: a novel method for preparing protein nanoparticles for protein therapy. International journal of pharmaceutics. 2011;403(1-2):192-200. 152. Li X, Anton N, Arpagaus C, Belleteix F, Vandamme TF. Nanoparticles by spray drying using innovative new technology: The Büchi Nano Spray Dryer B-90. Journal of Controlled Release. 2010;147(2):304-10. 153. Schmid K, Arpagaus C, Friess W. Evaluation of the Nano Spray Dryer B-90 for pharmaceutical applications. Pharm Dev Technol. 2011;16(4):287-94. 154. Mulla JA, Mabrouk M, Choonara YE, Kumar P, Chejara DR, du Toit LC, et al. Development of respirable rifampicin-loaded nano-lipomer composites by microemulsion-spray drying for pulmonary delivery. Journal of Drug Delivery Science and Technology. 2017;41:13-9. 155. Beck-Broichsitter M, Schweiger C, Schmehl T, Gessler T, Seeger W, Kissel T. Characterization of novel spray-dried polymeric particles for controlled pulmonary drug delivery. Journal of controlled release. 2012;158(2):329-35. 156. Bürki K, Jeon I, Arpagaus C, Betz G. New insights into respirable protein powder preparation using a nano spray dryer. International Journal of Pharmaceutics. 2011;408(1-2):248-56. 157. Lee SH, Heng D, Ng WK, Chan H-K, Tan RBH. Nano spray drying: A novel method for preparing protein nanoparticles for protein therapy. International Journal of Pharmaceutics. 2011;403(1):192-200. 158. Vukkum P, Moses Babu J, Muralikrishna R. Stress Degradation Behavior of Atorvastatin Calcium and Development of a Suitable Stability-Indicating LC Method for the Determination of Atorvastatin, its Related Impurities, and its Degradation Products. Scientia Pharmaceutica. 2013;81(1):93-114. 159. Lea AP, McTavish D. Atorvastatin. A review of its pharmacology and therapeutic potential in the management of hyperlipidaemias. Drugs. 1997;53(5):828-47. 160. Sonje VM, Kumar L, Meena CL, Kohli G, Puri V, Jain R, et al. Chapter 1 - Atorvastatin Calcium. In: Brittain HG, editor. Profiles of Drug Substances, Excipients and Related Methodology. 35: Academic Press; 2010. p. 1-70. 161. Fisher M, Moonis M. Neuroprotective Effects of Statins: Evidence from Preclinical and Clinical Studies. Current Treatment Options in Cardiovascular Medicine. 2012;14(3):252-9. 162. Lennernas H. Clinical pharmacokinetics of atorvastatin. Clinical pharmacokinetics. 2003;42(13):1141-61. 163. Nacar OA, Eroglu H, Cetinalp NE, Menekse G, Yildirim AE, Uckun OM, et al. Systemic administration of atorvastatin improves locomotor functions and hyperacute-acute response after experimental spinal cord injury: an ultrastructural and biochemical analysis. Turkish neurosurgery. 2014;24(3):337-43. 164. Eroglu H, Nemutlu E, Turkoglu OF, Nacar O, Bodur E, Sargon MF, et al. A quadruped study on chitosan microspheres containing atorvastatin calcium: preparation, characterization, quantification and in-vivo application. Chemical and Pharmaceutical Bulletin. 2010;58(9):1161-7. 165. Pan HC, Yang DY, Ou YC, Ho SP, Cheng FC, Chen CJ. Neuroprotective effect of atorvastatin in an experimental model of nerve crush injury. Neurosurgery. 2010;67(2):376-88; discussion 88-9. 166. Nazli Y, Colak N, Alpay MF, Uysal S, Uzunlar AK, Cakir O. Neuroprotective effect of atorvastatin in spinal cord ischemia-reperfusion injury. Clinics (Sao Paulo, Brazil). 2015;70(1):52-60. 167. Ewen T, Qiuting L, Chaogang T, Tao T, Jun W, Liming T, et al. Neuroprotective Effect of Atorvastatin Involves Suppression of TNF-α and Upregulation of IL-10 in a Rat Model of Intracerebral Hemorrhage. Cell Biochemistry and Biophysics. 2013;66(2):337-46. 168. Bösel J, Gandor F, Harms C, Synowitz M, Harms U, Djoufack PC, et al. Neuroprotective effects of atorvastatin against glutamate‐induced excitotoxicity in primary cortical neurones. Journal of Neurochemistry. 2005;92(6):1386-98. 169. Barone E, Cenini G, Di Domenico F, Martin S, Sultana R, Mancuso C, et al. Long-term high-dose atorvastatin decreases brain oxidative and nitrosative stress in a preclinical model of Alzheimer disease: A novel mechanism of action. Pharmacological Research. 2011;63(3):172-80. 170. Song T, Liu J, Tao X, Deng J. Protection effect of atorvastatin in cerebral ischemia-reperfusion injury rats by blocking the mitochondrial permeability transition pore. Genet Mol Res. 2014;13(4):10632-42. 171. Gomes MB, Negrato CA. Alpha-lipoic acid as a pleiotropic compound with potential therapeutic use in diabetes and other chronic diseases. Diabetology & metabolic syndrome. 2014;6(1):80. 172. Nichols Jr T. Alpha-lipoic acid: biological effects and clinical implications. Altern Med Rev. 1997;2(177):83. 173. Bilska A, Wlodek L. Lipoic acid-the drug of the future. Pharmacol Rep. 2005;57(5):570-7. 174. Kofuji K, Isobe T, Murata Y. Controlled release of alpha-lipoic acid through incorporation into natural polysaccharide-based gel beads. Food chemistry. 2009;115(2):483-7. 175. Golbidi S, Badran M, Laher I. Diabetes and Alpha Lipoic Acid. Frontiers in Pharmacology. 2011;2:69. 176. Slemmer JE, Shacka JJ, Sweeney MI, Weber JT. Antioxidants and free radical scavengers for the treatment of stroke, traumatic brain injury and aging. Curr Med Chem. 2008;15(4):404-14. 177. Luoma AM, Kuo F, Cakici O, Crowther MN, Denninger AR, Avila RL, et al. Plasmalogen phospholipids protect internodal myelin from oxidative damage. Free Radical Biology and Medicine. 2015;84:296-310. 178. Toklu HZ, Hakan T, Celik H, Biber N, Erzik C, Ogunc AV, et al. Neuroprotective effects of alpha-lipoic acid in experimental spinal cord injury in rats. The journal of spinal cord medicine. 2010;33(4):401-9. 179. Senoglu M, Nacitarhan V, Kurutas EB, Senoglu N, Altun I, Atli Y, et al. Intraperitoneal Alpha-Lipoic Acid to prevent neural damage after crush injury to the rat sciatic nerve. Journal of Brachial Plexus and Peripheral Nerve Injury. 2009;4:22-. 180. Guideline IHT, editor Validation of analytical procedures: text and methodology Q2 (R1). International Conference on Harmonization, Geneva, Switzerland; 2005. 181. Guideline IHT. Stability testing of new drug substances and products. Q1A (R2), current step. 2003;4:1-24. 182. Food, Administration D. Guidance for industry Q1A (R2) stability testing of new drug substances and products. Food and Drug Administration, Rockville, MD(Online) http://www fda gov/downloads/RegulatoryInformation/Guidances/ucm128204 pdf. 2003. 183. Zhou X-B, Zou D-X, Gu W, Wang D, Feng J-S, Wang J-Y, et al. An Experimental Study on Repeated Brief Ischemia in Promoting Sciatic Nerve Repair and Regeneration in Rats. World Neurosurgery. 2018;114:e11-e21. 184. Dinh P, Hazel A, Palispis W, Suryadevara S, Gupta R. Functional assessment after sciatic nerve injury in a rat model. Microsurgery. 2009;29(8):644-9. 185. Thalhammer JG, Vladimirova M, Bershadsky B, Strichartz GR. Neurologic evaluation of the rat during sciatic nerve block with lidocaine. Anesthesiology. 1995;82(4):1013-25. 186. Koka R, Hadlock TA. Quantification of functional recovery following rat sciatic nerve transection. Experimental neurology. 2001;168(1):192-5. 187. Kerns JM, Braverman B, Mathew A, Lucchinetti C, Ivankovich AD. A comparison of cryoprobe and crush lesions in the rat sciatic nerve. Pain. 1991;47(1):31-9. 188. Wu J, Yang H, Qiu Z, Zhang Q, Ding T, Geng D. Effect of combined treatment with methylprednisolone and Nogo-A monoclonal antibody after rat spinal cord injury. Journal of International Medical Research. 2010;38(2):570-82. 189. Jafari SM. Nanoencapsulation Technologies for the Food and Nutraceutical Industries: Academic Press; 2017. 190. Brinkmann-Trettenes U, Barnert S, Bauer-Brandl A. Single step bottom-up process to generate solid phospholipid nano-particles. Pharmaceutical development and technology. 2014;19(3):326-32. 191. Bürki K, Jeon I, Arpagaus C, Betz G. New insights into respirable protein powder preparation using a nano spray dryer. International Journal of Pharmaceutics. 2011;408(1):248-56. 192. Beck-Broichsitter M, Strehlow B, Kissel T. Direct fractionation of spray-dried polymeric microparticles by inertial impaction. Powder Technology. 2015;286:311-7. 193. Shin YM, Hohman MM, Brenner MP, Rutledge GC. Experimental characterization of electrospinning: the electrically forced jet and instabilities. Polymer. 2001;42(25):09955-67. 194. Kim JI, Hwang TI, Aguilar LE, Park CH, Kim CS. A Controlled Design of Aligned and Random Nanofibers for 3D Bi-functionalized Nerve Conduits Fabricated via a Novel Electrospinning Set-up. Scientific Reports. 2016;6:23761. 195. Behrens AM, Kim J, Hotaling N, Seppala JE, Kofinas P, Tutak W. Rapid fabrication of poly(DL-lactide) nanofiber scaffolds with tunable degradation for tissue engineering applications by air-brushing. Biomedical materials (Bristol, England). 2016;11(3):035001. 196. Reul R, Renette T, Bege N, Kissel T. Nanoparticles for paclitaxel delivery: a comparative study of different types of dendritic polyesters and their degradation behavior. International journal of pharmaceutics. 2011;407(1-2):190-6. 197. Sayin B, Calis S. Influence of accelerated storage conditions on the stability of vancomycin-loaded poly (d, l-lactide-co-glycolide) microspheres. FABAD J Pharm Sci. 2004;29:111-6. 198. de Medinaceli L, Freed WJ, Wyatt RJ. An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks. Exp Neurol. 1982;77(3):634-43. 199. Gudemez E, Ozer K, Cunningham B, Siemionow K, Browne E, Siemionow M. Dehydroepiandrosterone as an enhancer of functional recovery following crush injury to rat sciatic nerve. Microsurgery. 2002;22(6):234-41. 200. Oliveira EF, Mazzer N, Barbieri CH, Selli M. Correlation between functional index and morphometry to evaluate recovery of the rat sciatic nerve following crush injury: experimental study. Journal of reconstructive microsurgery. 2001;17(1):69-75. 201. Schiaveto de Souza A, Da Silva C, Del Bel E. Methodological evaluation to analyze functional recovery after sciatic nerve injury. Journal of neurotrauma. 2004;21(5):627-35. 202. Khan J, Noboru N, Young A, Thomas D. Pro and anti-inflammatory cytokine levels (TNF-alpha, IL-1beta, IL-6 and IL-10) in rat model of neuroma. Pathophysiology : the official journal of the International Society for Pathophysiology. 2017;24(3):155-9.tr_TR
dc.identifier.urihttp://hdl.handle.net/11655/5367
dc.descriptionThis study was supported by TÜBİTAK-1001 Scientific Project with the number 115 S 202.tr_TR
dc.description.abstractHAIDAR Mohammad Karim, Development of Nano-formulations Containing Neuroprotective Active Ingredient and Evaluation of Efficiency in Peripheral Nerve Injury Model, Hacettepe University Graduate School of Health Sciences, Ph.D. Thesis in Department of Biopharmaceutics and Pharmacokinetics, Ankara, 2018. Peripheral nerve injury (PNI) is one of the common traumas. Causes of acquired peripheral neuropathy include physical injury, diseases or disorders, exposure to toxins etc. Depending on nature and severity of injury, several therapeutic methods have been proposed. Crush injury is the most common type (80% of PNI) of PNI and decompression is the only way for treatment. However, the outcome of this treatment method is not satisfactory. Therefore, accelerating the curative process by additional treatment is strongly required. The aim of this thesis is to develop a novel polymeric composite nanofiber which containing nanoparticles for dual and localized delivery of neuroprotective drugs for accelerating regeneration process of peripheral nerve injury. For this purpose, alpha lipoic acid (ALA) and atorvastatin calcium (ATR) were used as neuroprotective agents. At first step ATR loaded chitosan nanoparticles were prepared by Nano Spray drying method. At the second step, Nano Spray dryed ATR loaded chitosan nanoparticles were suspended into solution of poly lactic-co-glycolic acid (PLGA) and ALA. The resulting mixture was exposed to electrospinning and electrospun nanocomposites were collected for further study. After characterization of these formulations, regrading to composition of formulation, selected formulation was used subsequently and implanted into animal model of sciatic nerve trauma. Trauma was formed with the compression method in Sprague Dawley rats. The motor function and sensory tests in the post-surgery stage revealed significant improvement in the regeneration process of nerve injury in the treated animals. The ultrastructural examination of sciatic nerve tissues samples at different timepoints also implies that the number of normal myelinated axons were increased in the treatment groups. The determination of pro-inflammatory cytokines also supported the effectiveness of the developed formulation. As the conclusion of this study, we might state that ATR loaded chitosan nanoparticles that are embedded in ALA containing nanofibers could be promising drug delivery systems for neuroprotection after peripheral sciatic nerve injury, especially depending on the faster recovery within the first 15 days period after trauma.en
dc.description.sponsorshiptubitaktr_TR
dc.description.tableofcontentsCONFIRMATION PAG. iii YAYIMLAMA VE FİKRİ MÜLKİYET HAKLARI BEYANI iv ETHICAL DECLARATIO v ACKNOWLEDGEMENTS vi ABSTRACT vii ÖZET viii CONTENTS ix SYMBOLS AND ABBREVIATIONS xv FIGURES xvii TABLES xxi 1. INTRODUCTION 1 2. GENERAL INFORMATION 3 2.1.HUMAN NERVOUS SYSTEM 3 2.2.PERIPHERAL NERVOUS SYSTEM 3 2.3.NERVOUS SYSTEM CELL 4 2.3.1 Neuron 4 2.3.2 Types of Neurons 5 2.3.3 Neuroglia 8 2.4. PERIPHERAL NERVE FIBERS 9 2.5. ACTION POTENTIAL 13 2.6. PERIPHERAL NERVE INJURY 14 2.6.1 Classification 15 2.6.2 Response of Nerve After Injury 17 2.6.3 Inflammatory Response 19 2.6.4 Nerve Regeneration 20 2.7. NANOFIBER 22 2.7.1 Fabrication of Polymeric Nanofibers 23 2.7.2 Electrospinning Technique 24 2.7.3 Electrospinning Variables 25 2.7.4 Physical Strength of Nanofibrous Scaffold 28 2.7.5 Degradation of Nanofibers 28 2.7.6 Drug Loading into Nanofibers 29 2.7.7 Post-Treatment of Nanofibers 29 2.7.8 Electrospinning of Blend Drugs and Polymer 30 2.7.9 Coaxial Electrospinning 30 2.7.10 Emulsion Electrospinning 31 2.7.11 Electrospinning Setup Modification 31 2.7.12 Drug Release Kinetics 32 2.7.13 Application 33 2.7.14 Drug Delivery Applications 33 2.7.15 Local Delivery of Antibiotics Other Than Wound-Dressing Purposes 35 2.7.16 Antibiotic Loaded Nanofibers for Wound Dressings Applications 35 2.7.17 Local Delivery of Chemotherapeutic Agents 36 2.8. PREPARATION TECHNIQUES OF POLYMERIC NANOPARTICLES 37 2.8.1 Nanoprecipitation (Solvent Displacement) 38 2.8.2 Coacervation Method 38 2.8.3 Ionic Gelation Method 39 2.8.4 Preparation of Polymeric Nanoparticle Based on The Emulsification. 39 2.8.5 W/O Emulsification 40 2.8.6 Emulsification-Solvent Evaporation 40 2.8.7 Emulsification-Solvent Diffusion 40 2.8.8 Salting-Out Method 41 2.8.9 Nano Spray Drying Method 41 2.9. NEUROPROTECTIVE DRUGS 44 2.9.1 Atorvastatin Calcium 44 2.9.2 Alpha Lipoic Acid 46 3. MATERIALS AND METHODS 49 3.1. MATERIALS AND EQUIPMENT 49 3.1.1 Chemical Reagents 49 3.1.2 Equipment 50 3.2. METHODS 51 3.2.1 Development and Validation of Revers Phase-High Performance Liquid Chromatography System Method for ALA and ATR 51 3.2.2 Selection of Initial RP-HPLC Conditions for Simultaneous Quantitative Analysis of ALA and ATR 51 3.2.3 Preparation of Buffer and Stock Solution 51 3.2.4 Method Validation 52 3.2.5 Formulation of Atorvastatin Loaded Chitosan Nanoparticles by Nano Spray Drying Method 55 3.2.6 Preparation of Atorvastatin Calcium/Chitosan Nanoparticles 55 3.2.7 Nanoparticle Characterization 57 3.2.8 In-Vitro Release Studies ATR loaded CH Nanoparticles 59 3.2.9 Cell Culture Studies 59 3.3. OPTIMIZATION OF ELECTROSPINNING PARAMETERS FOR PLGA NANOFIBER. 60 3.4. FABRICATION OF POLY (LACTIC-CO-GLYCOLIC ACID) (PLGA) AND CH ELECTROSPUN COMPOSITE NANOFIBER 62 3.4.1 Characterization of PLGA/CH Electrospun Composite Nanofiber Formulation 63 3.4.2 In-Vitro Release Studies of PLGA/CH Composite Nanofiber Sheet 66 3.4.3 Cytotoxicity Studies of PLGA/CH Composite Nanofiber Sheet. 66 3.4.4 Stability Test 67 3.5. IN-VIVO EXPERIMENTS 68 3.5.1 Experimental Groups and Surgical Procedure 68 3.5.2 Surgical Procedure 68 3.5.3 Assessment of Functional Recovery 70 3.5.4 Ultrastructural Examination 72 3.6. BIOCHEMICAL ANALYSIS 73 3.6.1 Preparation of Samples 73 3.6.2 Determination of TNF-α, IL-1β and IL-6 Levels 73 3.7. IN-VITRO MODELS OF NEUROTRAUMA/ORGANOTYPIC SPINAL CORD CULTURE 74 3.8. STATISTICAL ANALYSIS 75 4. RESULTS 76 4.1. RP-HPLC METHOD DEVELOPMENT AND VALIDATION 76 4.1.1 Instrument Precision (Injector Repeatability) 78 4.1.2 Linearity and Range 78 4.1.3 Sensitivity 80 4.1.4 Precision and Accuracy 80 4.1.5 Specificity (Selectivity) 81 4.1.6 Robustness 82 4.1.7 Stability Test 86 4.2. FORMULATION OF ATORVASTATIN LOADED CHITOSAN NANOPARTICLES BY NANO SPRAY DRYING METHOD 86 4.2.1 Characterization of Chitosan Nanoparticles 86 4.2.2 In-Vitro Release Studies 92 4.2.3 Cell Viability 93 4.3. OPTIMIZATION OF ELECTROSPINNING PARAMETERS FOR PLGA NANOFIBER 96 4.4. CHARACTERIZATION OF PLGA/CH ELECTROSPUN NANOCOMPOSITE 101 4.4.1 Morphology 101 4.4.2 Encapsulation Efficiency 103 4.4.3 Differential Scanning Calorimetry Analysis-DSC. 103 4.4.4 X-Ray Analysis. 105 4.4.5 FT-IR. 106 4.4.6 Porosity Measurements. 108 4.4.7 Texture Analysis 109 4.5. IN-VITRO RELEASE STUDIES OF ALA AND ATR FROM COMPOSITE NANOFIBER FORMULATION 110 4.6. CELL VIABILITY OF ELECTRO SPUN NANOCOMPOSITES FORMULATIONS 111 4.7. STABILITY TEST 112 4.8. IN-VIVO EXPERIMENTS 114 4.8.1 Sciatic Functional Index (SFI) 114 4.8.2 Behavioral Testing (BBB). 116 4.8.3 Extensor Postural Thrust Test (EPT). 117 4.8.4 Withdrawal Reflex Latency (WRL). 118 4.8.5 Ultrastructural Examination. 120 4.8.6 Determination of TNF-α , IL-1β and IL-6 Levels 123 4.9. EX VIVO MODELS OF NEUROTRAUMA/ORGANOTYPIC SPINAL CORD CULTURE 124 5. DISCUSSION 130 5.1. ANALYTICAL METHOD VALIDATION 130 5.2. FORMULATION OF ATORVASTATIN LOADED CHITOSAN NANOPARTICLES BY NANO SPRAY DRYING METHOD 131 5.2.1 Characterization of ATR loaded CH Nanoparticles 132 5.2.2 In-vitro Release 134 5.2.3 Cytotoxicity of CH Nanoparticles 135 5.3. POLY LACTIC-CO-GLYCOLIC ACID/CHITOSAN ELECTROSPUN NANO COMPOSITE 135 5.3.1 Preparation and Morphological Characteristic 135 5.3.2 Encapsulation and In-Vitro Drug Release 136 5.3.3 Physicochemical Analysis of Electrospun PLGA/CH Nanocomposite 137 5.3.4 Porosity Measurements 137 5.3.5 Texture Analysis 138 5.3.6 Cell Viability of Electrospun Nanocomposites Formulations 138 5.3.7 Stability Test 138 5.3.8 In-Vivo Study 139 5.3.9 Functional Assessments 139 5.3.10 TEM Examination of Sciatic Nerve Samples 141 5.3.11 Determination of TNF-α, IL-1β and IL-6 Levels 142 6. CONCLUSION 144 7. REFERENCES 146 8. APPANDICES 160 8.1. CURRICULUM VITAE 160 8.2. ETHICAL COMMITTEE APPROVAL 163 8.3. DIGITAL RECEIPT FOR TORNITIN REPORT 164tr_TR
dc.language.isoengtr_TR
dc.publisherSağlık Bilimleri Enstitüsütr_TR
dc.rightsinfo:eu-repo/semantics/closedAccesstr_TR
dc.subjectAtorvastatin Calciumtr_TR
dc.subjectAlpha Lipoic Acid
dc.subjectNanoparticle
dc.subjectNanofiber
dc.subjectPeripheral Nerve Injury
dc.subjectCell Culture
dc.titleDevelopment of Nano-Formulatıons Contaınıng Neuroprotectıve Actıve Ingredıent and Evaluatıon of Effıcıency in Perıpheral Nerve Injury Modelen
dc.typedoctoralThesisen
dc.description.ozetHAIDAR Mohammad Karim, Nöroprotektif etkin madde içeren nanoformülasyonların geliştirilmesi ve periferik sinir hasarı modelinde etkinliklerinin değerlendirilmesi, Hacettepe Üniversitesi Sağlık Bilimleri Enstitüsü Biyofarmasötik ve Farmakokinetik Programı Doktora Tezi, Ankara, 2018. Periferik Sinir Hasarı (PSH), en sık görülen travma türleri arasında yer almaktadır. Oluşum sebepleri arasında fiziksel yaralanma, hastalıklar ve toksinlere maruziyet gibi çok sayıda sebep bulunmaktadır. Yaralanmanın türü ve şiddetine bağlı olarak farklı tedavi yaklaşımları bulunmaktadır. Çarpma hasarı, PSH türleri arasında en sık görülen türü (%80) olmakla birlikte tedavi için tek yok uygulanan basının kaldırılmasıdır. Buna karşın uygulanan bu tedavinin çıktıları çoğu zaman yeterli olmamaktadır. Dolayısı ile ek tedavi yöntemleri ile tedavi sürecinin hızlandırılması ihtiyacı vardır. Bu çalışmanın amacı, periferik sinir hasarında rejenerasyon sürecini hızlandırmak için nöroprotektif etkin maddelerin ikili ve lokalize salımını sağlayacak içerisinde nanopartikül içeren kompozit polimerik nanofiber hazırlamaktır. Bu amaçla nöroprotektif etkin maddeler olarak alfa lipoik asit (ALA) ve atorvastatin kalsiyum (ATR) kullanılmıştır. İlk aşamada ATR içeren nanopartiküller nanopüskürterek kurutma cihazında hazırlanmış; ikinci aşamada ise hazırlanan bu nanopartiküller, içerisinde ALA ve poli(laktik-ko-glikolik)asit içeren çözeltide süspande edilmiştir. Oluşturulan bu karışım, elektrospinleme ile kompozit nanofiberlerin hazırlanmasında kullanılmıştır. Formülasyonların karakterizasyon aşamasını takiben, seçilen uygun formülasyon, siyatik sinir hasarı oluşturulmuş hayvan modelinde implante edilmiştir. Sprague-Dawley cinsi sıçanlarda kompresyon yöntemi ile siyatik sinir hasarı oluşturulmuştur. Cerrahi sonrası dönemde gerçekleştirilen motor fonksiyon ve duyusal testler sonucunda deney hayvanlarında sinir hasarında anlamlı bir düzelme olduğu görülmüştür. Buna ek olarak yapılan ultrastrüktürel incelemeler sonucunda da tedavi gruplarında normal miyelinli akson sayılarındaki artış tespit edilmiştir. Pro-inflamatuvar sitokinler üzerinde yapılan incelemelerde elde edilen bulgular geliştirilen formülasyonun etkinliğini destekleyici nitelikte sonuçlanmıştır. Sonuç olarak içerisinde ATR yüklü nanopartiküller gömülmüş olan ALA içeren nanofiberlerin periferik sinir hasarı sonrasında nöroproteksiyon amaçlı, özellikle de travma sonrasındaki ilk 15 günlük dönem içerisinde, kullanılabilecek uygun ilaç taşıyıcı sistemler olduğu düşünülmektedir.tr_TR
dc.contributor.departmentFarmasötik Teknolojitr_TR
dc.contributor.authorID10220937tr_TR
dc.embargo.terms2 yiltr_TR
dc.embargo.lift2020-11-14T11:19:04Z


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record