電刺激-響應藥物釋放水凝膠

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姓名	張翌暐(Yi-Wei Chang) 查詢紙本館藏	畢業系所	化學工程與材料工程學系
論文名稱	電刺激-響應藥物釋放水凝膠 (Electrical stimulation-responsive drug release hydrogels)
檔案	[Endnote RIS 格式] [Bibtex 格式] [相關文章] [文章引用] [完整記錄] [館藏目錄] 至系統瀏覽論文 (2027-7-27以後開放)
摘要(中)	在本研究我們開發了一種電刺激響應水凝膠。我們利用合成將F127改質使其端基具苯磺酸官能基的三嵌段共聚物SF127。將F127與SF127依不同比例混合形成表面具苯磺酸官能基微胞，並透過裝載匹洛西卡(Piroxicam)藥物於微胞內成為藥物載體。再加入導電高分子PEDOT:PSS使其形成具複合導電水凝膠，並可應用貼片式電刺激藥物釋放材料。我們使用示差熱掃描分析DSC，複合導電水凝膠的臨界微包溫度 (TCMT) 和臨界溶膠-凝膠溫度 (TSGT)，也利用小角 X 光散射 (SAXS) 量測奈米載體封裝藥物前後微胞尺寸變化。此外，通過結合流變儀和小角 X 光散射SAXS (Rheo-SAXS) 即時原位量測，探討導電水凝膠在線性和非線性流變學中的黏彈性行為和微胞排列(體心立方(FCC)和六方堆積(HCP))方式的變化與電刺激藥物釋放之關係。
摘要(英)	In this study we developed an electrical stimulation-responsive hydrogel. We synthesized the triblock copolymer (SF127), modified by poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol), F127, so that its end groups had benzenesulfonic acid functional groups. F127 and SF127 were mixed in different ratios to form micelles with benzenesulfonic acid functional groups on the surface, and the micelles were loaded with Piroxicam to become a drug carrier. Subsequently, the conductive polymer PEDOT:PSS is added to form a composite conductive hydrogel, and a patch-type electrostimulation drug release material can be applied. Critical micelle temperature (TCMT) and critical sol-gel temperature (TSGT) of composite conducting hydrogels are measured by differential thermal scanning to analyze DSC, and the micelle size changes before and after drug encapsulation in nanocarriers are measured by small-angle X-ray scattering (SAXS). Furthermore, by combining a rheometer and small-angle X-ray scattering SAXS (Rheo-SAXS) instant in situ measurements, we investigate the relationship between the viscoelastic behavior of conductive hydrogels in linear and nonlinear rheology and the changes in the arrangement of micelles (body-centered cubic (FCC) and hexagonal packing (HCP)) with electrically stimulated drug release.
關鍵字(中)	★ 電刺激響應 ★ 藥物釋放 ★ 水凝膠 ★ 小角度X-ray散射	關鍵字(英)
論文目次	目錄中文摘要 I Abstract II 誌謝 III 目錄 IV 圖目錄 VII 表目錄 X 第一章緒論 1 第二章文獻回顧 2 2.1 藥物傳輸系統 (Drug delivery systems, DDS) 2 2.1.2 A-B-A三嵌段共聚物(F127) 8 2.2 流變學研究 10 2.2.1 Oscillation amplitude sweep 10 2.2.2 小振幅震盪剪切 (SAOS) 11 2.2.3 大振幅振盪剪切 (LAOS) 12 2.3 導電高分子PEDOT:PSS 15 2.3.1 PEDOT:PSS發展歷程 15 2.3.2 PEDOT:PSS 之層級結構 16 2.3.3 PEDOT:PSS生物相容性 18 2.4 研究動機 19 第三章實驗 20 3.1 實驗藥品及儀器 20 3.1.1 實驗藥品 20 3.1.2 實驗儀器 21 3.2 實驗製備 22 3.2.1 合成SF127 22 3.2.2 FS複合水凝膠之製備 24 3.2.3 FSP複合導電水凝膠之製備 24 3.2.4 Piroxicam (PX)之藥物封裝 25 3.2.5 FS/FSP水凝膠熱性質量測 26 3.2.6 FS/FSP (PX)水凝膠藥物釋放樣品配置 26 3.2.7 分子模擬 26 3.3實驗儀器 27 3.3.1 液態超導核磁共振儀(Nuclear Magnetic Resonance Spectrometer, NMR) 27 3.3.2 傅立葉變換紅外光譜儀(Fourier-transform infrared spectrometer, FTIR) 28 3.3.3 掃描式微分熱卡計 (Differential Scanning Calorimeter, DSC) 29 3.3.4 流變儀 (Strain-controlled rheometer) 29 3.3.5 小角度X-ray散射 (SAXS) 30 3.3.6 擬合軟體 (Sasview) 31 3.3.7 紫外-可見光光譜分析儀 (UV-Vis spectrometer) 32 3.3.8 膠體導電度測定 32 第四章結果與討論 34 4.1 SF127合成(苯磺酸官能化F127) 34 4.2 FS複合水凝膠和FSP複合導電水凝膠的熱性質分析 38 4.2.1 苯磺酸官能化SF127對F127微胞形成的影響 38 4.2.2 PEDOT:PSS混摻對微胞化的影響 40 4.3 FSP複合導電水凝膠導電度 42 4.4 FS及FSP複合型水凝膠之Piroxicam (PX)藥物釋放系統分析 43 4.4.1 PX溶於甲醇之檢量線製作 43 4.4.2 探討藥物載體F20S0及F18S2對PX包覆率之影響 44 4.4.3 探討包覆PX對藥物載體F20S0及F18S2微胞尺寸影響 46 4.4.4 PX溶於磷酸鹽緩衝生理鹽水之檢量線製作 48 4.4.5 FSP水凝膠體外電刺激釋放PX之分析 49 4.5 結合流變儀及小角度 X-ray 散射探討FS及FSP水凝膠之流變行為及其微結構變化 52 4.5.1 F127水凝膠流變特性及微結構變化 52 4.5.2 SF127混摻對F127水凝膠流變特性及微結構之影響 55 4.5.3 PEDOT:PSS混摻對FS水凝膠流變特性及微結構之影響 58 結論 62 參考文獻 63
參考文獻	參考文獻 (1) Ge, J.; Neofytou, E.; Cahill, T. J.; Beygui, R. E.; Zare, R. N. Drug Release from Electric-Field-Responsive Nanoparticles. ACS Nano 2012, 6, 227−233. (2) Benoit, D.S.; Overby, C.T.; Sims, K.R., Jr.; Ackun-farmmer, M.A. Drug Delivery Systems (Ch. 2.5.12). Biomaterials Science: An Introduction to Materials in Medicine (Fourth Edition); Elsevier: Amsterdam, The Netherlands, 2020, 1237–1266. (3) Vargason, A. M.; Anselmo, A. C.; Mitragotri, S. The Evolution of Commercial Drug Delivery Technologies. Nat. Biomed. Eng. 2021, 5, 951–967. (4) Yuk, H.; Lu, B.; Zhao, X. Hydrogel Bioelectronics. Chem. Soc. Rev. 2019, 48, 1642–1667. (5) Hu, W.; Wang, Z.; Xiao, Y.; Zhang, S.; Wang, J. Advances in Crosslinking Strategies of Biomedical Hydrogels. Biomater. Sci. 2019, 7, 843–855. (6) Lavrador, P.; Esteves, M. R.; Gaspar, V. M.; Mano, J. F. Stimuli‐Responsive Nanocomposite Hydrogels for Biomedical Applications. Adv. Funct. Mater. 2020, 31, 2005941. (7) Li, J.; Mooney, D. J. Designing Hydrogels for Controlled Drug Delivery. Nat. Rev. Mater. 2016, 1, 16071. (8) Lee, Y., Chung, H. J., Yeo, S., Ahn, C. H., Lee, H., Messersmith, P. B., & Park, T. G. Thermo-sensitive, injectable, and tissue adhesive sol–gel transition hyaluronic acid/pluronic composite hydrogels prepared from bio-inspired catechol-thiol reaction. Soft Matter 2010, 6(5), 977-983. (9) Russo, E.; Villa, C. Poloxamer Hydrogels for Biomedical Applications. Pharmaceutics 2019, 11, 671. (10) Morishita, M.; Barichello, J. M.; Takayama, K.; Chiba, Y.; Tokiwa, S.; Nagai, T. Pluronic® F-127 Gels Incorporating Highly Purified Unsaturated Fatty Acids for Buccal Delivery of Insulin. Int. J. Pharm. 2001, 212, 289–293. (11) Kadam, Y.; Yerramilli, U.; Bahadur, A. Solubilization of Poorly Water-Soluble Drug Carbamezapine in Pluronic® Micelles: Effect of Molecular Characteristics, Temperature and Added Salt on the Solubilizing Capacity. Colloids Surf., B 2009, 72, 141–147. (12) Taha, E. I.; Badran, M. M.; El-Anazi, M. H.; Bayomi, M. A.; El-Bagory, I. M. Role of Pluronic F127 Micelles in Enhancing Ocular Delivery of Ciprofloxacin. J. Mol. Liq. 2014, 199, 251–256. (13) Jaiswal, M.; Kumar, M.; Pathak, K. Zero Order Delivery of Itraconazole via Polymeric Micelles Incorporated In Situ Ocular Gel for the Management of Fungal Keratitis. Colloids Surf., B 2015, 130, 23–30. (14) Wang, G.; Nie, Q.; Zang, C.; Zhang, B.; Zhu, Q.; Luo, G.; Wang, S. Self-Assembled Thermoresponsive Nanogels Prepared by Reverse Micelle→Positive Micelle Method for Ophthalmic Delivery of Muscone, a Poorly Water-Soluble Drug. J. Pharm. Sci. 2016, 105, 2752–2759. (15) Jung, Y.-S.; Park, W.; Park, H.; Lee, D.-K.; Na, K. Thermo-Sensitive Injectable Hydrogel Based on the Physical Mixing of Hyaluronic Acid and Pluronic F-127 for Sustained NSAID Delivery. Carbohydr. Polym. 2017, 156, 403–408. (16) Zhang, C.; Zhang, J.; Qin, Y.; Song, H.; Huang, P.; Wang, W.; Wang, C.; Li, C.; Wang, Y.; Kong, D. Co-Delivery of Doxorubicin and Pheophorbide A by Pluronic F127 Micelles for Chemo-Photodynamic Combination Therapy of Melanoma. J. Mater. Chem. B 2018, 6, 3305–3314. (17) Hyun, K.; Wilhelm, M.; Klein, C. O.; Cho, K. S.; Nam, J. G.; Ahn, K. H.; Lee, S. J.; Ewoldt, R. H.; McKinley, G. H. A Review of Nonlinear Oscillatory Shear Tests: Analysis and Application of Large Amplitude Oscillatory Shear (LAOS). Prog. Polym. Sci. 2011, 36, 1697–1753. (18) Schreuders, F. K. G.; Sagis, L. M. C.; Bodnár, I.; Erni, P.; Boom, R. M.; van der Goot, A. J. Small and Large Oscillatory Shear Properties of Concentrated Proteins. Food Hydrocoll. 2021, 110, 106172. (19) Ewoldt, R. H.; Hosoi, A. E.; McKinley, G. H. New Measures for Characterizing Nonlinear Viscoelasticity in Large Amplitude Oscillatory Shear. J. Rheol. 2008, 52, 1427–1458. (20) Kleber, C.; Lienkamp, K.; Ruhe, J.; Asplund, M. Electrochemically Controlled Drug Release from a Conducting Polymer Hydrogel (PDMAAp/PEDOT) for Local Therapy and Bioelectronics. Adv. Healthc. Mater. 2019, 8, 1801488. (21) Groenendaal, L.; Jonas, F.; Freitag, D.; Pielartzik, H.; Reynolds, J. R. Poly (3, 4‐ethylenedioxythiophene) and Its Derivatives: Past, Present, and Future. Adv. Mater. 2000, 12, 481–494. (22) Kayser, L. V.; Lipomi, D. J. Stretchable Conductive Polymers and Composites Based on PEDOT and PEDOT:PSS. Adv. Mater. 2019, 31, 1806133. (23) Takano, T.; Masunaga, H.; Fujiwara, A.; Okuzaki, H.; Sasaki, T. PEDOT Nanocrystal in Highly Conductive PEDOT:PSS Polymer Films. Macromolecules 2012, 45, 3859–3865. (24) Zhang, S.; Chen, Y.; Liu, H.; Wang, Z.; Ling, H.; Wang, C.; Ni, J.; Celebi-Saltik, B.; Wang, X.; Meng, X.; Kim, H. J.; Baidya, A.; Ahadian, S.; Ashammakhi, N.; Dokmeci, M. R.; Travas-Sejdic, J.; Khademhosseini, A. Room-Temperature-Formed PEDOT:PSS Hydrogels Enable Injectable, Soft, and Healable Organic Bioelectronics. Adv. Mater. 2020, 32, 1904752. (25) Fani, N.; Hajinasrollah, M.; Asghari Vostikolaee, M.; Baghaban Eslaminejad, M.; Mashhadiabbas, F.; Tongas, N.; Rasoulianboroujeni, M.; Yadegari, A.; Ede, K.; Tahriri, M. Influence of Conductive PEDOT: PSS in a Hard Tissue Scaffold: In Vitro and In Vivo Study. J. Bioact. Compat. Polym. 2019, 34, 436–441. (26) Balding, P.; Borrelli, R.; Volkovinsky, R.; Russo, P. S. Physical Properties of Sodium Poly(styrene sulfonate): Comparison to Incompletely Sulfonated Polystyrene. Macromolecules 2022, 55, 1747–1762. (27) Braglia, M.; Ferrari, I. V.; Djenizian, T.; Kaciulis, S.; Soltani, P.; Di Vona, M. L.; Knauth, P. Bottom-Up Electrochemical Deposition of Poly(styrene sulfonate) on Nanoarchitectured Electrodes. ACS Appl. Mater. Interfaces 2017, 9, 22902–22910. (28) Taylor, D. K.; Jayes, F. L.; House, A. J.; Ochieng, M. A. Temperature-Responsive Biocompatible Copolymers Incorporating Hyperbranched Polyglycerols for Adjustable Functionality. J. Funct. Biomater. 2011, 2, 173–194. (29) Maeda, Y.; Higuchi, T.; Ikeda, I. FTIR Spectroscopic and Calorimetric Studies of the Phase Transitions of N-Isopropylacrylamide Copolymers in Water. Langmuir 2001, 17, 7535–7539. (30) Bonacucina, G.; Spina, M.; Misici-Falzi, M.; Cespi, M.; Pucciarelli, S.; Angeletti, M.; Palmieri, G. F. Effect of Hydroxypropyl β-Cyclodextrin on the Self-Assembling and Thermogelation Properties of Poloxamer 407. Eur. J. Pharm. Sci. 2007, 32, 115–122. (31) Pragatheeswaran, A. M.; Chen, S. B. Effect of Chain Length of PEO on the Gelation and Micellization of the Pluronic F127 Copolymer Aqueous System. Langmuir 2013, 29, 9694–9701.
指導教授	孫亞賢莊偉綜(Ya-Sen Sun Wei-Tsung Chuang)	審核日期	2022-7-27
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