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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳進庭(Chin-Tin Chen) | |
| dc.contributor.author | Yun-Tien Ko | en |
| dc.contributor.author | 柯蘊恬 | zh_TW |
| dc.date.accessioned | 2022-11-25T03:04:22Z | - |
| dc.date.available | 2024-07-07 | |
| dc.date.copyright | 2021-08-18 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-07-30 | |
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Motwani, S., et al., Chitosan–sodium alginate nanoparticles as submicroscopic reservoirs for ocular delivery: Formulation, optimisation and in vitro characterisation. European Journal of Pharmaceutics and Biopharmaceutics, 2007. 40. Zimmer, A. and J. Kreuter, Microspheres and nanoparticles used in ocular delivery systems. Advanced Drug Delivery Reviews, 1995. 16(1): p. 61-73. 41. Subasranjan, A. and R. Hemant, An improved validated ultra high pressure liquid chromatography method for separation of tacrolimus impurities and its tautomers. Drug testing and analysis, 2010. 2(3): p. 107-112. 42. Lallemand, F., et al., Successfully improving ocular drug delivery using the cationic nanoemulsion, novasorb. Journal of drug delivery, 2012. 2012. 43. Garrett, Q., et al., Carboxymethylcellulose binds to human corneal epithelial cells and is a modulator of corneal epithelial wound healing. Investigative ophthalmology visual science, 2007. 48(4): p. 1559-1567. 44. Mansuri, S., et al., Mucoadhesion: A promising approach in drug delivery system. Reactive and functional polymers, 2016. 100: p. 151-172. 45. Shaikh, R., et al., Mucoadhesive drug delivery systems. Journal of Pharmacy and Bioallied Sciences, 2011. 3(1): p. 89. 46. Eshel-Green, T. and H. Bianco-Peled, Mucoadhesive acrylated block copolymers micelles for the delivery of hydrophobic drugs. Colloids and Surfaces B: Biointerfaces, 2016. 139: p. 42-51. 47. Friuli, V., et al., Influence of dissolution media and presence of alcohol on the in vitro performance of pharmaceutical products containing an insoluble drug. Journal of pharmaceutical sciences, 2018. 107(1): p. 507-511. 48. Vaishya, R.D., et al., Controlled ocular drug delivery with nanomicelles. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 2014. 6(5): p. 422-437. 49. Partearroyo, M.A., et al., Surfactant-induced cell toxicity and cell lysis: a study using B16 melanoma cells. Biochemical pharmacology, 1990. 40(6): p. 1323-1328. 50. Li, M., et al., New nanomicelle curcumin formulation for ocular delivery: improved stability, solubility, and ocular anti-inflammatory treatment. Drug development and industrial pharmacy, 2017. 43(11): p. 1846-1857. 51. Song, K., et al., Novel ultra-small micelles based on rebaudioside A: a potential nanoplatform for ocular drug delivery. International journal of pharmaceutics, 2018. 552(1-2): p. 265-276. 52. Guo, C., et al., Nanomicelle formulation for topical delivery of cyclosporine A into the cornea: in vitro mechanism and in vivo permeation evaluation. Scientific reports, 2015. 5(1): p. 1-14. 53. Souto, E.B., et al., Advanced formulation approaches for ocular drug delivery: State-of-the-art and recent patents. Pharmaceutics, 2019. 11(9): p. 460. 54. Mojaddam, M. and K.R. Pullen, Optimization of a centrifugal compressor using the design of experiment technique. Applied Sciences, 2019. 9(2): p. 291. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81821 | - |
| dc.description.abstract | 由於眼睛自身的保護機制，眼藥的遞送仍是一大挑戰。眼睛的物理屏障由淚膜、角膜和結膜所構成，不論是親水性或疏水性藥物的滲透都受到了阻礙；而淚液的分泌也導致藥物無法長時間停留在眼睛表面，使得眼藥的生體可利用率 (bioavailability) 僅有 5 %，甚至更低；因此眼藥的遞送為重要的研究課題。 Tacrolimus (TAC) 源自一土壤菌叢 Streptomyces tsukubaensis，最初用來預防移植手術引起的排斥反應；現今可針對乾眼症、春季性結膜炎等發炎症狀來做治療。近年來，許多研究開發利用懸浮液 (suspensions)、軟膏 (ointments)、奈米顆粒 (nanoparticles) 等載體來遞送TAC 至眼睛。考量 TAC 在水中的低溶解度、病患對於藥物的依順性 (compliance) 及藥物的滲透性，本研究選擇微胞 (micelles) 作為開發的劑型，並透過增稠劑的添加來延長藥物停留在眼睛表面的時間。 本研究重點在於 TAC 微胞劑型的開發與優化，首先依據美國食品藥物管理局 (FDA) 的資料庫從中篩選賦形劑來進行實驗設計，為符合規範及因應安全性考量須調整滲透壓及酸鹼值。之後於比較有無添加增稠劑兩種組成的差異時，發現有添加增稠劑組別的黏度有顯著的增加，並於藥物釋放的結果中得到較緩慢的釋放速率；另外，根據細胞毒性試驗的結果，劑型組成顯示具有低細胞毒性，而以細胞攝入的試驗結果得到，添加增稠劑至劑型中並不會影響細胞對於藥物的攝入。 本研究開發出能承載 TAC 的微胞溶液並證實這一劑型的安全性，未來可透過動物實驗，進一步驗證溶液的黏度對於眼藥停留在眼表的影響，同時藉由控制藥物釋放的速率，來達到提升眼藥生體可利用率的目的。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-25T03:04:22Z (GMT). No. of bitstreams: 1 U0001-2807202123203200.pdf: 3062212 bytes, checksum: d67237ae200efa716747dc073a9ce415 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | 口試委員會審定書 i 謝辭 ii 中文摘要 iii 英文摘要 iv 目錄 vi 圖目錄 viii 表目錄 ix 第一章、 研究背景 1 1.1 Tacrolimus 1 1.2 眼睛生理學 3 1.3 眼用製劑 (Ophthalmic preparations) 5 1.4 微胞 (micelles) 7 1.5 增稠劑 (viscosity enhancers) 8 1.6 實驗設計 (design of experiments) 9 1.7 研究動機與目的 13 第二章、 材料與方法 14 2.1 藥品與儀器 14 2.2 細胞株 (Cell lines) 18 2.3 實驗方法 20 2.3.1 Tacrolimus-loaded 微胞開發及劑型優化 20 2.3.2 Tacrolimus 定量分析 22 2.3.3 微胞特性分析 23 2.3.4 安定性試驗 24 2.3.5 體外藥物釋放試驗 24 2.3.6 體外細胞毒性測定 26 2.3.7 體外細胞攝入試驗 27 2.4 統計方法 28 第三章、 結果 29 3.1 Tacrolimus-loaded 微胞開發、劑型優化及特性分析 29 3.2 增稠劑添加對劑型之影響 32 3.3 Tacrolimus 定量分析 35 3.4 Tacrolimus微胞溶液黏度測定 36 3.5 安定性試驗 37 3.6 體外藥物釋放試驗 37 3.7 體外細胞毒性測定 39 3.8 體外細胞攝入試驗 40 第四章、 討論 41 4.1 Tacrolimus-loaded 微胞溶液製備與其特性分析 41 4.2 增稠劑對於Tacrolimus微胞溶液黏度的影響與評估 43 4.3 微胞溶液於室溫貯放下的安定性評估 44 4.4 添加增稠劑對於藥物釋放之影響 45 4.5 透過細胞毒性試驗評估微胞溶液之安全性 46 4.6 添加增稠劑對於細胞攝入之影響 47 第五章、 結論 49 第六章、 未來發展 50 參考文獻 90 附錄 96 | |
| dc.language.iso | zh-TW | |
| dc.subject | 眼藥遞送 | zh_TW |
| dc.subject | 劑型開發 | zh_TW |
| dc.subject | 眼藥水 | zh_TW |
| dc.subject | Tacrolimus | zh_TW |
| dc.subject | 微胞 | zh_TW |
| dc.subject | eye drops | en |
| dc.subject | micelles | en |
| dc.subject | Tacrolimus | en |
| dc.subject | ocular drug delivery | en |
| dc.subject | formulation development | en |
| dc.title | Tacrolimus 眼用微胞劑型之開發 | zh_TW |
| dc.title | Development of Ophthalmic Tacrolimus-loaded Micellar Formulations | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 吳亘承(Hsin-Tsai Liu),謝堅銘(Chih-Yang Tseng) | |
| dc.subject.keyword | 微胞,Tacrolimus,眼藥遞送,劑型開發,眼藥水, | zh_TW |
| dc.subject.keyword | micelles,Tacrolimus,ocular drug delivery,formulation development,eye drops, | en |
| dc.relation.page | 111 | |
| dc.identifier.doi | 10.6342/NTU202101873 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2021-07-30 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科技學系 | zh_TW |
| dc.date.embargo-lift | 2024-07-07 | - |
| 顯示於系所單位： | 生化科技學系 | |
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