臺灣博碩士論文加值系統

刺激響應之藥物傳遞系統 (Stimuli-responsive drug delivery systems) 是一種新穎的藥物遞送方式，此種方法可以藉由外在的刺激來控制藥物釋放的情形。其中壓電材料被視為一種可以藉由外力刺激產生電訊號回饋而最終促進藥物載體釋放藥物的材料。在本研究中，我們使用以還原氧化石墨烯 (reduced graphene oxide) 及聚醚酰亞胺 (polyetherimide) 改質的聚偏二氟乙烯 (poly(vinylidene fluoride-co-hexafluoropropylene)) 以旋轉塗佈的方式製備成壓電多層薄膜，其中還原氧化石墨烯及聚醚酰亞胺的加入提升了薄膜的壓電性質以及修飾了其表面型態。接著將壓電多層薄膜以滴注的方式重複製作層狀的聚烯丙基胺鹽酸鹽 (poly(allylamine hydrochloride)) 以及聚乙二胺樹枝狀高分子 (poly(amido amine)) 作為藥物載體，另外使用4,4'-二疊氮-磺酸二鈉鹽四水合物 (4,4’-diazido- 2,2’-stilbenedisulfonic acid disodium) 進行光交聯反應，以增加薄膜的穩定性。最後在材料最外層以電紡絲的方式製作聚甲基丙烯酸羥基乙酯 (poly(2-hydroxyethyl methacrylate)) 微米薄膜以增加材料對身體組織的貼附性。實驗結果表示，這種新型貼片具有高達 68% 的 β 相比率和均勻的表面。與滴落塗佈的傳統方法相比，旋轉塗佈製作的貼片表現出高靈敏度之壓電響應。它可以在 20 mmHg 的外力下產生壓電輸出。材料製備完成後，我們對材料進行細胞毒性測試，結果顯示材料具有良好的生物相容性，可以運用在不同的病症和疾病。

Stimuli-responsive drug delivery system is a novel strategy that allows for the controlled release of drugs through external stimuli. Among these systems, piezoelectric materials are reported to be able generate electrical stimulation in response to external forces, thereby promoting the release of drugs from the drug carrier. In this study, poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) which is one of the piezoelectric materials was mixed with reduced graphene oxide-polyetherimide (rGO-PEI) and prepared by spin-coating method as the substrate. The rGO-PEI could enhance the piezoelectric property and improve the surface roughness. The substrate was coated layer-by-layer with poly(allylamine hydrochloride) (PAH) and poly(amido amine) (PAMAM) as a drug reservoir, then 4,4’-diazido- 2,2’-stilbenedisulfonic acid disodium (DAS) was used for photo-crosslinking to enhance stability. Poly(2-hydroxyethyl methacrylate) (p[HEMA]) microfibers, which was prepared by electrospinning, was designed as the contacting layer to enhance the mucoadhesion. The results revealed that this novel patch with the high β phase ratio of 68% and a homogeneous surface. The spin-coated patch showed a high sensitivity response than the patch that prepared drop-casting method. The developed patch could generate the piezoelectric response at 20 mmHg. After the material preparation was completed, in vitro biocompatibility of developed patches was evaluated by cell viability. Based on the results, the developed composite patch with piezoelectric response properties could be applied in various biomedical fields due to it well biocompatibility.

中文摘要 I
Abstract II
Acknowledgments III
Content IV
List of figures VII
List of tables X
Chapter 1 Introduction 1
1.1 Foreword 1
1.2 Motivation and purpose 1
Chapter 2 Literature review and theory 3
2.1 Enhance drug release by piezoelectricity 3
2.2 Piezoelectricity 4
2.2.1 Direct piezoelectric effect 4
2.2.2 Inverse piezoelectric effect 5
2.3 Poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) 6
2.4 Thin film techniques 8
2.4.1 Blade-coating 9
2.4.2 Drop-casting 9
2.4.3 Spin-coating 11
2.5 Electrospinning technology 12
2.6 Poly(hydroxyethyl methacrylate) (p[HEMA]) 14
2.7 Layer-by-layer (LbL) technique 15
Chapter 3 Experimental section 17
3.1 Materials 17
3.2 Instruments 19
3.3 Experimental procedure 21
3.4 Preparation of the rGPP piezoelectric multilayers 22
3.4.1 Synthesis of rGO-PEI 22
3.4.2 Preparation of rGPP solution 22
3.4.3 Substrate cleaning process 23
3.4.4 Manufacture rGPP piezoelectric multilayers 23
3.5 Preparation of the LbL PAH/PAMAM multilayers 24
3.5.1 Preparation of PAH and PAMAM solution 24
3.5.2 PAH/PAMAM LbL multilayer assembly 25
3.6 Preparation of electrospun p[HEMA] 26
3.6.1 Preparation p[HEMA] solution 26
3.6.2 Prepare of p[HEMA] microfiber 26
3.7 Prepartion of rGPP piezoelectric patch 27
3.8 Characterization 28
3.8.1 Contact angle measurement 28
3.8.2 Fourier-transform infrared spectroscopy analysis 28
3.8.3 Calculation of PEI loss 29
3.8.4 Piezoelectric response analysis 29
3.8.5 β-phase fraction analysis 30
3.8.6 UV-Vis spectrophotometer 31
3.8.7 Morphology 32
3.8.8 Thickness measurement 33
3.8.9 Swelling test 33
3.8.10 Tensile test 34
3.9 Cell culture 35
3.10 In vitro bioavailability 36
3.11 Statistical analysis 37
Chapter 4 Results and discussion 38
4.1 Contact angle 38
4.2 Synthetic result of rGO-PEI 39
4.2.1 Fourier-transform infrared spectroscopy analysis 39
4.2.2 Calculation of PEI loss 41
4.3 Piezoelectric response analysis 42
4.4 UV-vis spectra of the assembly of 8-S-rGPP multilayers 50
4.5 β-phase fraction analysis 51
4.6 Morphology of rGPP films and multilayers 52
4.7 Morphology of p[HEMA] microfiber 54
4.8 Thickness measurement 56
4.9 Swelling test 57
4.10 UV-vis spectra of the assembly of (PAH/PAMAM)10.5 multilayers 59
4.11 Tensile test 61
4.12 In vitro bioavailability 63
Chapter 5 Conclusion 65
References 67

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