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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78756完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 楊台鴻 | zh_TW |
| dc.contributor.author | 張庭瑄 | zh_TW |
| dc.contributor.author | Ting-Hsuan Chang | en |
| dc.date.accessioned | 2021-07-11T15:17:09Z | - |
| dc.date.available | 2024-07-30 | - |
| dc.date.copyright | 2019-08-01 | - |
| dc.date.issued | 2019 | - |
| dc.date.submitted | 2002-01-01 | - |
| dc.identifier.citation | 1. Rufer, F., A. Schroder, and C. Erb, White-to-white corneal diameter - Normal values in healthy humans obtained with the orbscan II topography system. Cornea, 2005. 24(3): p. 259-261.
2. Nishida, T., Neurotrophic Mediators and Corneal Wound Healing. The Ocular Surface, 2005. 3(4): p. 194-202. 3. Ambekar, R., K.C. Toussaint, and A.W. Johnson, The effect of keratoconus on the structural, mechanical, and optical properties of the cornea. Journal of the Mechanical Behavior of Biomedical Materials, 2011. 4(3): p. 223-236. 4. Sorkin, N. and D. Varssano, Corneal Collagen Crosslinking: A Systematic Review. Ophthalmologica, 2014. 232(1): p. 10-27. 5. Romero-Jiménez, M., J. Santodomingo-Rubido, and J.S. Wolffsohn, Keratoconus: A review. Contact Lens and Anterior Eye, 2010. 33(4): p. 157-166. 6. Subasinghe, S.K., K.C. Ogbuehi, and G.J. Dias, Current perspectives on corneal collagen crosslinking (CXL). Graefes Archive for Clinical and Experimental Ophthalmology, 2018. 256(8): p. 1363-1384. 7. Raiskup, F. and E. Spoerl, Corneal Crosslinking with Riboflavin and Ultraviolet A. Part II. Clinical Indications and Results. Ocular Surface, 2013. 11(2): p. 93-108. 8. Kamaev, P., et al., Photochemical kinetics model of corneal cross-linking with riboflavin. Investigative Ophthalmology & Visual Science, 2015. 56(7). 9. Mastropasqua, L., Collagen cross-linking: when and how? A review of the state of the art of the technique and new perspectives. Eye and Vision, 2015. 2. 10. Wollensak, G., E. Spoerl, and T. Seiler, Riboflavin/ultraviolet-A-induced collagen crosslinking for the treatment of keratoconus. American Journal of Ophthalmology, 2003. 135(5): p. 620-627. 11. Schumacher, S., L. Oeftiger, and M. Mrochen, Equivalence of Biomechanical Changes Induced by Rapid and Standard Corneal Cross-linking, Using Riboflavin and Ultraviolet Radiation. Investigative Ophthalmology & Visual Science, 2011. 52(12): p. 9048-9052. 12. Beshtawi, I.M., et al., Biomechanical Properties of Human Corneas Following Low- and High-Intensity Collagen Cross-Linking Determined With Scanning Acoustic Microscopy. Investigative Ophthalmology & Visual Science, 2013. 54(8): p. 5273-5280. 13. Elbaz, U., et al., Accelerated (9-mW/cm(2)) Corneal Collagen Crosslinking for Keratoconus-A 1-Year Follow-up. Cornea, 2014. 33(8): p. 769-773. 14. Rawas-Qalaji, M. and C.A. Williams, Advances in Ocular Drug Delivery. Current Eye Research, 2012. 37(5): p. 345-356. 15. Ghate, D. and H.F. Edelhauser, Barriers to Glaucoma Drug Delivery. Journal of Glaucoma, 2008. 17(2): p. 147-156. 16. Ali, M. and M.E. Byrne, Challenges and solutions in topical ocular drug- delivery systems. Expert Review of Clinical Pharmacology, 2008. 1(1): p. 145-161. 17. Drug Delivery and Targeting for Pharmacists and Pharmaceutical Scientists, ed. L.A. Hillery AA, Swarbick J. 2001, New York: Taylor and Francis Inc. 18. Vandamme, T.F., Microemulsions as ocular drug delivery systems: recent developments and future challenges. Progress in Retinal and Eye Research, 2002. 21(1): p. 15-34. 19. Fialho, S.L. and A. da Silva-Cunha, New vehicle based on a microemulsion for topical ocular administration of dexamethasone. Clinical and Experimental Ophthalmology, 2004. 32(6): p. 626-632. 20. Rathore, K. and R.K. Nema, Review on ocular inserts. Vol. 1. 2009. 164-169. 21. Singh, R.R.T., et al., Minimally invasive microneedles for ocular drug delivery. Expert Opinion on Drug Delivery, 2017. 14(4): p. 525-537. 22. Henry, S., et al., Microfabricated microneedles: A novel approach to transdermal drug delivery (vol 87, pg 922, 1998). Journal of Pharmaceutical Sciences, 1999. 88(9): p. 948-948. 23. Ryan F. Donnelly, T.R.R.S., Desmond I. J. Morrow, A. David Woolfson, Microneedle-mediated Transdermal and Intradermal Drug Delivery. 2012. 24. Gaudana, R., et al., Ocular Drug Delivery. Aaps Journal, 2010. 12(3): p. 348-360. 25. Kim, Y.C., J.H. Park, and M.R. Prausnitz, Microneedles for drug and vaccine delivery. Advanced Drug Delivery Reviews, 2012. 64(14): p. 1547-1568. 26. Hong, X.Y., et al., Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine. Drug Design Development and Therapy, 2013. 7: p. 945-952. 27. Ye, Y.Q., et al., Polymeric microneedles for transdermal protein delivery. Advanced Drug Delivery Reviews, 2018. 127: p. 106-118. 28. Sullivan, S.P., N. Murthy, and M.R. Prausnitz, Minimally invasive protein delivery with rapidly dissolving polymer microneedles. Advanced Materials, 2008. 20(5): p. 933-+. 29. Santos, L.F., et al., Biomaterials for drug delivery patches. European Journal of Pharmaceutical Sciences, 2018. 118: p. 49-66. 30. Dupps, W.J. and S.E. Wilson, Biomechanics and wound healing in the cornea. Experimental Eye Research, 2006. 83(4): p. 709-720. 31. Komai, Y. and T. Ushiki, The three-dimensional organization of collagen fibrils in the human cornea and sclera. Investigative Ophthalmology & Visual Science, 1991. 32(8): p. 2244-2258. 32. Wollensak, G. and E. Iomdina, Long-term biomechanical properties of rabbit cornea after photodynamic collagen crosslinking. Acta Ophthalmologica, 2009. 87(1): p. 48-51. 33. Hatami-Marbini, H. and A. Rahimi, Stiffening effects of riboflavin/UVA corneal collagen cross-linking is hydration dependent. Journal of Biomechanics, 2015. 48(6): p. 1052-1057. 34. Mackiewicz, Z., et al., Collagenolytic proteinases in keratoconus. Cornea, 2006. 25(5): p. 603-610. 35. Goosey, J.D., J.S. Zigler, Jr., and J.H. Kinoshita, Cross-linking of lens crystallins in a photodynamic system: a process mediated by singlet oxygen. Science, 1980. 208(4449): p. 1278-80. 36. Spoerl, E., G. Wollensak, and T. Seiler, Increased resistance of crosslinked cornea against enzymatic digestion. Current Eye Research, 2004. 29(1): p. 35-40. 37. Schilde, T., et al., Depth dependence of stiffening on riboflavin/UVA treated corneas. Investigative Ophthalmology & Visual Science, 2005. 46: p. 1. 38. Gilger, B.C., et al., Treatment of Acute Posterior Uveitis in a Porcine Model by Injection of Triamcinolone Acetonide Into the Suprachoroidal Space Using Microneedles. Investigative Ophthalmology & Visual Science, 2013. 54(4): p. 2483-2492. 39. Jiang, J., et al., Coated microneedles for drug delivery to the eye. Investigative Ophthalmology & Visual Science, 2007. 48(9): p. 4038-4043. 40. Quinn, H.L., et al., Design of a Dissolving Microneedle Platform for Transdermal Delivery of a Fixed-Dose Combination of Cardiovascular Drugs. Journal of Pharmaceutical Sciences, 2015. 104(10): p. 3490-3500. 41. Park, S.H., et al., Microneedle-based minimally-invasive measurement of puncture resistance and fracture toughness of sclera. Acta Biomaterialia, 2016. 44: p. 286-294. 42. Thakur, R.R.S., et al., Rapidly dissolving polymeric microneedles for minimally invasive intraocular drug delivery. Drug Delivery and Translational Research, 2016. 6(6): p. 800-815. 43. Wollensak, G., et al., Keratocyte cytotoxicity of riboflavin/UVA-treatment in vitro. Eye, 2004. 18(7): p. 718-722. 44. Hayes, S., et al., The Effect of Riboflavin/UVA Collagen Cross-linking Therapy on the Structure and Hydrodynamic Behaviour of the Ungulate and Rabbit Corneal Stroma. Plos One, 2013. 8(1): p. 12. 45. Girard, M.J.A., et al., Scleral Biomechanics in the Aging Monkey Eye. Investigative Ophthalmology & Visual Science, 2009. 50(11): p. 5226-5237. 46. Chu, L.Y., S.-O. Choi, and M.R. Prausnitz, Fabrication of Dissolving Polymer Microneedles for Controlled Drug Encapsulation and Delivery: Bubble and Pedestal Microneedle Designs. Journal of Pharmaceutical Sciences, 2010. 99(10): p. 4228-4238. 47. Lee, I.C., et al., Fabrication of a novel partially dissolving polymer microneedle patch for transdermal drug delivery. Journal of Materials Chemistry B, 2015. 3(2): p. 276-285. 48. Larraneta, E., et al., Microneedle arrays as transdermal and intradermal drug delivery systems: Materials science, manufacture and commercial development. Materials Science & Engineering R-Reports, 2016. 104: p. 1-32. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78756 | - |
| dc.description.abstract | 眼角膜膠原蛋白交聯利用核黃素/紫外線搭配刮除角膜上皮，已被視為有效延緩圓錐角膜惡化及其他角膜疾病的療法。在本篇研究中，利用可溶性微針突破角膜上皮屏障將核黃素導入角膜，微針由生物相容性材料製作而成，並在實驗中測試微針穿刺角膜的能力及穿刺深度等特性，以及評估含藥微針角膜上之藥物穿透釋放能力及應用於膠原蛋白交聯術之效果，根據我們實驗的結果顯示，使用含有50%高分子且包裹0.6%核黃素的微針施行膠原蛋白交聯術，相較於滴核黃素溶液在角膜上，有較好的藥物穿透性，而在機械性質及抗酵素分解的能力上也有增加的效果。綜觀而言，本篇研究揭示了可溶性高分子微針的製作方法以及配方，證明其可成功地將水溶性藥物傳導入角膜基質中，因此，本研究之結果提供一個有發展潛力的工具，用於提高角膜膠原蛋白交聯手術效果以及病患順應性。 | zh_TW |
| dc.description.abstract | Corneal collagen cross-linking with Riboflavin/UVA coupling with corneal epithelium removal has already been recognized as effective therapy for limiting the progression of keratoconus and other corneal disorders. In the study, dissolving microneedles were used to bypass the corneal epithelium barrier enhancing ocular drug delivery of Riboflavin. MNs were fabricated using biocompatible materials, polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA) polymers, with conical shape and characterized for their insertion puncture forces and insertion depth. The MNs containing Riboflavin were investigated by in vitro drug permeation and corneal crosslinking effect comparing to topical application of Riboflavin solution. According to our results, 50% (w/w) PVP produced MNs containing 0.6% Riboflavin demonstrated high drug permeation with constant release comparing to topical applied aqueous solutions, an increase of tensile modulus and enzymatic digestion resistance comparing to untreated corneas. Overall, this study reported the fabrication and formulation of minimally invasive rapidly dissolving polymeric MNs which were able to efficiently deliver hydrophilic drug to the corneal stroma. Thus, it becomes potential manner to enhancing ocular delivery for improving efficiency and patient compliance to the corneal collagen crosslinking procedure. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T15:17:09Z (GMT). No. of bitstreams: 1 ntu-108-R06548012-1.pdf: 1195446 bytes, checksum: eb47ce22f9fcbaa5dc23b550e6f3d2bd (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | 誌謝 i
中文摘要 ii ABSTRACT iii CONTENTS iv LIST OF FIGURES vi LIST OF TABLES viii Chapter 1 Introduction 1 1.1 Corneal structures 1 1.2 Corneal collagen cross-linking 2 1.2.1 Keratoconus(KCN) 2 1.2.2 Riboflavin-induced collagen cross-linking 2 1.2.3 Corneal collagen cross-linking protocols in clinical practice 3 1.3 Ocular drug delivery 4 1.3.1 Barrier of ocular drug delivery 4 1.3.2 Administration routes to overcome ocular barriers 5 1.4 Minimally invasive microneedle arrays 6 1.5 Microneedles material properties 8 1.6 Evaluating the efficiency of corneal properties 9 1.6.1 Biomechanical properties 9 1.6.2 Enzymatic degradation 10 1.7 The Aim 10 Chapter 2 Materials and methods 12 2.1 Materials 12 2.2 Methods 12 2.2.1 Fabrication of dissolving MN arrays 12 2.2.1.1 Preparation of drug-loaded MN arrays 13 2.2.2 Microneedles characterization 13 2.2.3 Assessment of the insertion force in ocular tissues 13 2.2.4 In Vitro Drug Delivery Studies 14 2.2.5 Crosslinking procedures 14 2.2.6.1 Photo-induced cross-linking 15 2.2.6 Enzymatic digestion 15 2.2.7 Biomechanical measurements 16 2.2.8 Human corneal epithelial cell (HCEC) culture 16 2.2.9 Cell viability 16 2.2.10 Statistical analysis 17 Chapter 3 Results 18 3.1 Microneedles fabrication and characterization 18 3.2 Insertion forces and depth of microneedles 19 3.3 In vitro ocular drug delivery 20 3.4 CXL effect measurements 21 3.5 Cell viability 23 Chapter 4 Discussion 24 Chapter 5 Conclusion 27 FIGURES 28 Tables 35 REFERENCES 36 | - |
| dc.language.iso | en | - |
| dc.title | 利用可溶性微針包覆核黃素作為角膜藥物傳遞之工具 | zh_TW |
| dc.title | Dissolving Microneedles as a Potential Method for Ocular Drug Delivery of Riboflavin | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 107-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 王一中;李亦淇;黃琮瑋 | zh_TW |
| dc.contributor.oralexamcommittee | ;; | en |
| dc.subject.keyword | 核黃素/紫外線交聯術,微針陣列,眼角膜,高分子,生物機械性質, | zh_TW |
| dc.subject.keyword | Riboflavin/UVA crosslinking,Microneedles,Ocular drug delivery,Cornea,Polymer,Biomechanical strength, | en |
| dc.relation.page | 38 | - |
| dc.identifier.doi | 10.6342/NTU201901779 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2019-07-23 | - |
| dc.contributor.author-college | 工學院 | - |
| dc.contributor.author-dept | 醫學工程學系 | - |
| dc.date.embargo-lift | 2029-08-01 | - |
| 顯示於系所單位： | 醫學工程學研究所 | |
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