| 研究生: |
劉昱君 Liu, Yu-Jun |
|---|---|
| 論文名稱: |
探討利用薄膜過濾法一步驟製備甲殼素空心微針 Investigation of one-step fabrication of chitosan hollow microneedles by membrane filtration |
| 指導教授: |
莊怡哲
Juang, Yi-Je |
| 學位類別: |
碩士 Master |
| 系所名稱: |
工學院 - 化學工程學系 Department of Chemical Engineering |
| 論文出版年: | 2018 |
| 畢業學年度: | 106 |
| 語文別: | 中文 |
| 論文頁數: | 71 |
| 中文關鍵詞: | 生物可降解高分子 、中空微針 、薄膜過濾 、幾丁聚醣 、聚二甲基矽氧烷 、治療藥物監測 |
| 外文關鍵詞: | biodegradable polymer, hollow microneedles, membrane filtration, chitosan, polydimethylsiloxane, therapeutic drug monitoring |
| 相關次數: | 點閱:96 下載:12 |
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近年來,空心微針已被製造,並且應用於即時(point-of-care)經皮生物感測器或藥物輸送。與實心微針相比,空心微針的優點有二:一為允許更大藥物量被輸送,另一個為透過連接編程的微型幫浦,可以持續地主動控制藥物輸送。雖然大部分關於空心微針的研究主要為經皮藥物輸送裝置,但它們也可以作為微全分析系統(micro total analysis system, μTAS)以評估生物樣品,例如用於葡萄糖檢測的微型葡萄糖感測器、用於萬古黴素的微針-光流體(optofluidic)的生物感測器,以及用於監測谷氨酸的雙成份微針生物感測器。
本研究以微過濾的方式製作高分子空心微針貼片,首先製作出具有上下通孔的金字塔狀微結構陣列之PDMS模具,將模具放在濾紙上,並滴上chitosan溶液,開始抽氣過濾,一小時後可製作出chitosan空心微針。接著探討影響微針成形的因素,包括過濾時間、濾紙孔徑大小、高分子濃度,以及測試微針機械強度、穿刺豬皮等微針性質,也觀察微針在組成豬皮成分的明膠固化物中,其溶解形貌隨時間之變化。實驗結果顯示,所製作的空心chitosan微針並沒有足夠的強度能穿刺豬皮,可透過在空心微針內填入PVP,使成PVP-chitosan複合微針解決強度不夠的問題。而在親水性濾膜表面旋塗一層疏水性PDMS薄膜,可以製備流體僅由微針內空腔流通,而不由微針陣列間濾紙流過的微針貼片。
In this study, we proposed and demonstrated a one-step process to fabricate the polymer hollow microneedles (MNs) by filtration. The polydimethylsiloxane (PDMS) mold with funnel-like cavities with through holes was first created, which was placed on top of a filter paper. A droplet of chitosan solution was dispensed on top of the mold and vacuum was turned on. Different processing parameters such as filtration time, solution concentration, vacuum power, etc. are discussed. It was found that the polymer hollow MNs were formed after 1-hr filtration, followed by 12-hr drying. After spin coating the PDMS film on the hollow MNs array, a MNs patch can be prepared by passing the fluid only through the MNs. However, the MNs as fabricated don’t have sufficient mechanical strength to penetrate the porcine skin. The PVP-chitosan composite MNs were made by filtration. The PVP-chitosan composite MNs are strong enough to penetrate the pigskin.
[1] M. Miller, and E. Pisani, “The cost of unsafe injections,” Bulletin of the world health organization, vol. 77, no. 10, pp. 808, 1999.
[2] K. Walters, “Transdermal drug delivery,” Routes of Drug Administration: Topics in Pharmacy, vol. 2, pp. 78, 2013.
[3] M. R. Prausnitz, and R. Langer, “Transdermal drug delivery,” Nature biotechnology, vol. 26, no. 11, pp. 1261, 2008.
[4] 翁玟雯、陳宣雅、張展維、鄭奕帝(民100) The journal of taiwan pharmacy, vol.27,no. 3,pp.28-33,2011
[5] Y. W. Chien, P. R. Keshary, Y. C. Huang et al., “Comparative controlled skin permeation of nitroglycerin from marketed transdermal delivery systems,” Journal of pharmaceutical sciences, vol. 72, no. 8, pp. 968-970, 1983.
[6] K. van der Maaden, W. Jiskoot, and J. Bouwstra, “Microneedle technologies for (trans) dermal drug and vaccine delivery,” Journal of controlled release, vol. 161, no. 2, pp. 645-655, 2012.
[7] K. Subramanyan, M. Misra, S. Mukherjee et al., “Advances in the materials science of skin: a composite structure with multiple functions,” MRS bulletin, vol. 32, no. 10, pp. 770-778, 2007.
[8] Y. Shahzad, R. Louw, M. Gerber et al., “Breaching the skin barrier through temperature modulations,” Journal of Controlled Release, vol. 202, pp. 1-13, 2015.
[9] K. S. Paudel, M. Milewski, C. L. Swadley et al., “Challenges and opportunities in dermal/transdermal delivery,” Therapeutic delivery, vol. 1, no. 1, pp. 109-131, 2010.
[10] S. Henry, D. V. McAllister, M. G. Allen et al., “Microfabricated microneedles: a novel approach to transdermal drug delivery,” Journal of pharmaceutical sciences, vol. 87, no. 8, pp. 922-925, 1998.
[11] M. Wang, L. Hu, and C. Xu, “Recent advances in the design of polymeric microneedles for transdermal drug delivery and biosensing,” Lab on a Chip, vol. 17, no. 8, pp. 1373-1387, 2017.
[12] S. H. Bariya, M. C. Gohel, T. A. Mehta et al., “Microneedles: an emerging transdermal drug delivery system,” Journal of Pharmacy and Pharmacology, vol. 64, no. 1, pp. 11-29, 2012.
[13] S.-J. Paik, S. Byun, J.-M. Lim et al., “In-plane single-crystal-silicon microneedles for minimally invasive microfluid systems,” Sensors and Actuators A: Physical, vol. 114, no. 2-3, pp. 276-284, 2004.
[14] Y.-C. Kim, J.-H. Park, and M. R. Prausnitz, “Microneedles for drug and vaccine delivery,” Advanced drug delivery reviews, vol. 64, no. 14, pp. 1547-1568, 2012.
[15] A. A. Hamzah, N. A. Aziz, B. Y. Majlis et al., “Optimization of HNA etching parameters to produce high aspect ratio solid silicon microneedles,” Journal of Micromechanics and Microengineering, vol. 22, no. 9, pp. 095017, 2012.
[16] P. Yih, V. Saxena, and A. Steckl, “A review of SiC reactive ion etching in fluorinated plasmas,” physica status solidi (b), vol. 202, no. 1, pp. 605-642, 1997.
[17] S. Henry, D. V. McAllister, M. G. Allen et al., “Microfabricated microneedles: a novel approach to transdermal drug delivery,” Journal of pharmaceutical sciences, vol. 87, no. 8, pp. 922-925, 1998.
[18] J. D. Hamilton, “Fabrication and analysis of injection molded plastic microneedle arrays,” Georgia Institute of Technology, 2011.
[19] J. A. Matriano, M. Cormier, J. Johnson et al., “Macroflux® microprojection array patch technology: a new and efficient approach for intracutaneous immunization,” Pharmaceutical research, vol. 19, no. 1, pp. 63-70, 2002.
[20] W. Martanto, S. P. Davis, N. R. Holiday et al., “Transdermal delivery of insulin using microneedles in vivo,” Pharmaceutical research, vol. 21, no. 6, pp. 947-952, 2004.
[21] S. P. Sullivan, N. Murthy, and M. R. Prausnitz, “Minimally invasive protein delivery with rapidly dissolving polymer microneedles,” Advanced materials, vol. 20, no. 5, pp. 933-938, 2008.
[22] I.-C. Lee, J.-S. He, M.-T. Tsai et al., “Fabrication of a novel partially dissolving polymer microneedle patch for transdermal drug delivery,” Journal of Materials Chemistry B, vol. 3, no. 2, pp. 276-285, 2015.
[23] S. Yang, F. Wu, J. Liu et al., “Phase‐Transition Microneedle Patches for Efficient and Accurate Transdermal Delivery of Insulin,” Advanced Functional Materials, vol. 25, no. 29, pp. 4633-4641, 2015.
[24] J.-H. Park, M. G. Allen, and M. R. Prausnitz, “Polymer microneedles for controlled-release drug delivery,” Pharmaceutical research, vol. 23, no. 5, pp. 1008-1019, 2006.
[25] M.-C. Chen, S.-F. Huang, K.-Y. Lai et al., “Fully embeddable chitosan microneedles as a sustained release depot for intradermal vaccination,” Biomaterials, vol. 34, no. 12, pp. 3077-3086, 2013.
[26] B. Stoeber, and D. Liepmann, “Arrays of hollow out-of-plane microneedles for drug delivery,” Journal of microelectromechanical systems, vol. 14, no. 3, pp. 472-479, 2005.
[27] N. Baron, J. Passave, B. Guichardaz et al., “Investigations of development process of high hollow beveled microneedles using a combination of ICP RIE and dicing saw,” Microsystem Technologies, vol. 14, no. 9-11, pp. 1475-1480, 2008.
[28] S. P. Davis, W. Martanto, M. G. Allen et al., “Hollow metal microneedles for insulin delivery to diabetic rats,” IEEE Transactions on Biomedical Engineering, vol. 52, no. 5, pp. 909-915, 2005.
[29] M. Zhu, H. Li, X. Chen et al., “Silica needle template fabrication of metal hollow microneedle arrays,” Journal of Micromechanics and Microengineering, vol. 19, no. 11, pp. 115010, 2009.
[30] K. Lee, H. C. Lee, D. S. Lee et al., “Drawing lithography: three‐dimensional fabrication of an ultrahigh‐aspect‐ratio microneedle,” Advanced Materials, vol. 22, no. 4, pp. 483-486, 2010.
[31] R. F. Donnelly, K. Mooney, E. Caffarel-Salvador et al., “Microneedle-mediated minimally invasive patient monitoring,” Therapeutic drug monitoring, vol. 36, no. 1, pp. 10-17, 2014.
[32] S. A. Ranamukhaarachchi, C. Padeste, M. Dübner et al., “Integrated hollow microneedle-optofluidic biosensor for therapeutic drug monitoring in sub-nanoliter volumes,” Scientific reports, vol. 6, pp. 29075, 2016.
[33] P. M. Wang, M. Cornwell, and M. R. Prausnitz, “Minimally invasive extraction of dermal interstitial fluid for glucose monitoring using microneedles,” Diabetes technology & therapeutics, vol. 7, no. 1, pp. 131-141, 2005.
[34] C. G. Li, H.-A. Joung, H. Noh et al., “One-touch-activated blood multidiagnostic system using a minimally invasive hollow microneedle integrated with a paper-based sensor,” Lab on a Chip, vol. 15, no. 16, pp. 3286-3292, 2015.
[35] G. H. McKinley, L. E. Rodd, M. S. Oliverira et al., “Extensional flows of polymer solutions in microfluidic converging/diverging geometries,” Journal of Central South University of Technology, vol. 14, no. 1, pp. 6-9, 2007.
[36] M.-C. Chen, M.-H. Ling, K.-Y. Lai et al., “Chitosan microneedle patches for sustained transdermal delivery of macromolecules,” Biomacromolecules, vol. 13, no. 12, pp. 4022-4031, 2012.
[37] Y.-J. Juang, Y.-L. Deng, and I.-C. Lee, “Membrane filtration: An unconventional route for fabrication of the flexible and dissolvable, polymer microneedle patches,” Biomicrofluidics, vol. 10, no. 4, pp. 044108, 2016.
[38] 曾湘涵, 探討利用薄膜過濾法製備具可撓性之可溶性高分子微針貼片, 民105.06.
[39] B. Pramanick, S. O. Martinez-Chapa, and M. J. Madou, “Fabrication of Biocompatible Hollow Microneedles Using the C-MEMS Process for Transdermal Drug Delivery,” ECS Transactions, vol. 72, no. 1, pp. 45-50, 2016.
[40] H. Suzuki, T. Tokuda, and K. Kobayashi, “A disposable “intelligent mosquito” with a reversible sampling mechanism using the volume-phase transition of a gel,” Sensors and Actuators B: Chemical, vol. 83, no. 1-3, pp. 53-59, 2002.
[41] J. R. Windmiller, G. Valdés‐Ramírez, N. Zhou et al., “Bicomponent Microneedle Array Biosensor for Minimally‐Invasive Glutamate Monitoring,” Electroanalysis, vol. 23, no. 10, pp. 2302-2309, 2011.
[42] S. Aoyagi, H. Izumi, Y. Isono et al., “Laser fabrication of high aspect ratio thin holes on biodegradable polymer and its application to a microneedle,” Sensors and Actuators A: Physical, vol. 139, no. 1-2, pp. 293-302, 2007.
[43] H. Huang, and C. Fu, “Different fabrication methods of out-of-plane polymer hollow needle arrays and their variations,” Journal of Micromechanics and Microengineering, vol. 17, no. 2, pp. 393, 2007.