臺灣博碩士論文加值系統

本研究主要目的為利用電漿改質聚乳酸-聚甘醇酸共聚物(PLGA)，觀察表面性質對體外降解實驗的影響；藉由溶劑揮發法製成PLGA薄膜，並經由氧氣電漿及氧氣/六氟化硫電漿分別進行單面及雙面改質。將改質後的PLGA樣品置於磷酸鹽緩衝溶液中，控制溫度在37℃，進行體外降解實驗。實驗分成兩組進行：其中，第ㄧ組降解實驗中，不更換PBS，亦即不控制酸鹼值，在第二組降解實驗中，則將體外降解環境之酸鹼值控制在7~7.4之間，觀察PLGA降解情形。
由第ㄧ組實驗結果得知，未經電漿改質之PLGA降解速率最快；第二組實驗結果發現，電漿單面改質之PLGA樣品的降解速率與未改質之樣品的降解速率相當，而電漿氧氣雙面改質之PLGA具有最快的降解速率。再者，利用凝膠滲透層析儀(GPC)、熱重分析儀(TGA)及示差掃描量熱儀(DSC)分析，詳細探討PLGA降解之情形。由GPC結果發現，降解反應初期，會造成分子量的下降，但PLGA並沒有重量損失的情形；當降解時間變長，PLGA會有明顯的重量損失變化，且分子量也持續地減少。PLGA進行降解反應時，高分子材料會產生裂解而造成重量損失及分子量的改變，進而影響材料之熱性質的變化。利用TGA及DSC分析結果得知，降解反應後之PLGA分子量變少，導致熱裂解溫度及玻璃轉移溫度較低；隨著降解時間的增加，PLGA之熱裂解溫度與玻璃轉移溫度會呈逐漸遞減的狀態。

The goal of this work is to investigate the effects of surface hydrophilicity on the in vitro degradation of poly(DL-lactide-co-glycolide) (PLGA) by applying oxygen and sulfur hexafluoride (SF6) plasmas.. The PLGA films were fabricated by solvent evaporation technique and treated by plasmas for one-side and double-side, with or without pH control for the PLGA immersed solution. The experimental results showed that, for the non-pH controlled PLGA, the highest degradation rate is possessed by non plasma-treated PLGA film (control). On the other hand, for the controlled pH PLGA samples, higher degradation rate is achieved by double-side O2-plasma-treated PLGA film.
The degradation characteristics are analyzed by gel permeation chromatography (GPC), thermal gravimetric analysis (TGA), and differential scanning calorimetry (DSC). GPC results showed that, in the beginning phase of the degradation, the molecular weight decreases while the weight loss seems to be unaffected. Progressively, mature phase of degradation took place, resulting in increasing rate of weight loss. During this phase, the PLGA films suffered swelling, cracking, and hydrolysis which change their thermal properties. The thermal decomposition temperature (by TGA measurement) and glass transition temperature (DSC) decrease also in this phase.
In summary, the effect of plasma treatment on PLGA degradation is not significant enough to alter the degradation rate which indicates that the plasma modification only limits on the very top layer of surface (about 10 ~ 1000Å.) of materials. According to the experimental results, we conclude that the degradation mechanism is closely related to water uptake, molecular weight loss and change in thermal properties of PLGA.

【摘要】 I
【Abstract】 II
【誌謝】 III
【總目錄】 IV
【圖目錄】 VII
【表目錄】 XI
第一章 緒論 1
1.1前言 1
1.2研究目的與動機 3
第二章 文獻回顧 5
2-1 生物可降解高分子 5
2-1.1生物可降解高分子種類 5
2-1.2生物可降解高分子應用於生醫材料之條件 10
2-2 聚乳酸-甘醇酸共聚合物之介紹 11
2-2.1 聚乳酸-甘醇酸共聚合物作為載體或支架之應用 12
2-2.2 PLGA降解機制 15
2-3 影響PLGA降解速率的因素 16
2-3.1 PLGA組成成分對降解的影響 17
2-3.2 PLGA平均分子量(Mw)、結晶性(crystallinity)對降解的影響 17
2-3.3 PLGA樣品尺寸大小對降解的影響 18
2-3.4體外釋放溶液的pH值對降解的影響 19
2-3.5 溫度對降解的影響 19
2-4 電漿的定義 20
2-4-1 低溫電漿的特色 22
2-4-2 低溫電漿產生方式 23
2-4-3 利用低溫電漿進行高分子表面改質 23
2-4-4 氧氣電漿與六氟化硫電漿 23
第三章 實驗材料與方法 26
3.1 研究目的 26
3.2 儀器原理及方法 28
3.2.1接觸角(Contact angle) 28
3.2.2 凝膠滲透層析儀(Gel permeation chromatography, GPC) 28
3.2.3 熱重分析儀( Thermogravimetric analysis, TGA) 29
3.2.4 示差掃描量熱儀( Differential scanning calorimetry, DSC) 30
3.2.5 原子力顯微鏡(Atomic force Microscopy, AFM) 31
3.3 實驗材料 32
3.4 實驗儀器與器材設備 32
3.5體外降解環境之模擬 33
3.6薄膜巨觀現象觀察 33
第四章 結果與討論 36
[第一部分] 36
4-1 PLGA薄膜之物性/化性分析 36
4-1.1接觸角測量 37
4-1.2 原子力顯微鏡(AFM)分析 39
4-1.3 PLGA薄膜熱性質分析 41
[第二部分] 42
4-2 PLGA薄膜之降解性質測定 42
4-2.1 PLGA降解情形之探討 43
4-2.2 PLGA膨潤度 51
4-2.3凝膠滲透層析儀(GPC)分析 55
4-3 PLGA薄膜之降解熱性質分析 58
4-3.1熱重分析儀(TGA) 58
4-3.2示差掃描量熱儀(DSC)分析 65
第五章 結論與未來展望 75
5-1 結論 75
5-2 未來展望 76
第六章 參考文獻 77

1.李新中 生物材料之電漿表面改質技術. 2007.
2.Halleux A-MCaJ. Classification of biodegradable polymers. France, 2000.
3.L. E. Freed GV-N, R. J. Biron, D. B. Eagles, D. C. Lesnoy, S. K. Barlow, R. Langer. Biodegradable Polymer Scaffolds for Tissue Engineering. Bio/Technology 1994;12:689 - 693.
4.A. Linde PA, C. Dahlin , K. Bjurstam, Y. Sundin Osteopromotion: a soft-tissue exclusion principle using a membrane for bone healing and bone neogenesis. Periodontol 1993;64:1116-1128.
5.L. Lu CAG, A. G. Mikos. In vitro degradation of thin poly(DL-lactic-co-glycolic acid) films. 1999;46:236-244.
6.M. Vert GS, R. Engel, J. Coudane. Something new in the field of PLA/GA bioresorbable polymers? Controlled release 1998;53:85-92.
7.I. Grizzi HG, S. Li and M. Vert. Hydrolytic degradation of devices based on poly(DL-lactic acid) size-dependence. Biomaterials 1995;16:305-311.
8.Kalra RAGaB. Biodegradable polymers for the environment. Science 2002;297:803-807.
9.S. Li SM. Further investigations on the hydrolytic degradation of poly(DL-lactide). Biomaterials 1999;20:35-44.
10.J. W. Leenslag AJP, R. R. M. Bos, F. R. Rozema, G. Bioering. Resorbable materials of poly(L-lactide). 7. In vivo and in vitro degradation. Biomaterials 1987;8:311-314.
11.M. Yamaguchi TS, T. Kanamori. Surface modification of poly(L-lactic acid) affects initial cell attachment, cell morphology, and cell growth. Artif Organs 2004;7:187-193.
12.B. D. Ratner ASH, F. J. Schoen, J. E. Lemons. An Introduction to Materials in Medicine. Biomaterials Science 2004:105-107.
13.Belbella A, Vauthier C, Fessi H, Devissaguet JP, Puisieux F. In vitro degradation of nanospheres from poly(D, L-lactides) of different molecular weights and polydispersities. Pharmaceutics 1996;129:95-102.
14.Y. Wan XQ, J. Lu, C. Zhu, L. Wan, J. Yang, J. Bei, S. Wang. Characterization of surface property of poly(lactide-co-glycolide) after oxygen plasma treatment. Biomaterials 2004;25:4777-4783.
15.房性中. 試驗新知(之二十五)：AASHTO與ASTM材料規範之差異性對照及說明. 中華技術季刊第35期 1997.
16.R. Chandra RR. Biodegradable polymers. Progress in Polymer Science 1998;23:1273-1335.
17.Claes AAIaLE. In vitro biocompatibility of bioresorbable polymers : poly(L,DL-lactide) and poly (L-lactide-co-glycolide). Biomaterials 1996;7:631-639.
18.H. Akagi YY, A. Inagaki, T. Fujimura. Microsatellite DNA markers for rice chromosomes. TAG Theoretical and Applied Genetics 1996;93:1071-1077.
19.Bendix D. Chemical synthesis of polylactide and its copolymers for medical applications. Polymer degradation and stability 1998;59:129-135.
20.Guerin MVaP. Biodegradation aliphatic polyesters of the poly(hydroxyl acid)-type for temporary therapeutic applications. Biomaterials degradation 1991.
21.Bhattacharya M. Material properties of biodegradable polymers, 2000.
22.M. Matsui YK. Biodegradable fibers made of poly-lactic acid, 1996.
23.D. E. Cutright JDBaBP. Histologic comparison of polylactic and polyglycolic acid sutures. Oral Surgery 1971;32:165-173.
24.E. T. H. Vink KRR, D. A. Glassner, P. R. Gruber. Application of life cycle assessment to NatureworksTM poly(lactide) PLA production. Polymer Degradation and stability 2003;80:403-419.
25.P. A. Gunatillake aRA. Biodegradable synthetic polymers for tissue engineering. European Cells and Materials 2003;5:1-16.
26.Ikada HTaY. Blends of Aliphatic Polyesters. Physical properties and morphologies of solution-cast blends from poly(DL-lactide) and poly(ε-caprolactone). Polymer Science 1996;60:2367-2375.
27.Ltd N-IP. Biodegradable Plastics- Developments and Environmental Impacts. 2002.
28.S. Facco aCB. Mater-bi-starch based polymers. Biodegradable Plastics Conference 2000.
29.Dawes E. Novel Biodegradable Microbial Polymers, 1990.
30.M. Hakkarainen A-CAaSK. Weight loss and molecular weight changes correlated with the evolution of hydroxyacids in simulated in vivo degradation of homo- and copolymers of PLA and PGA. Polymer Degradation and Stability 1996;52:283-291.
31.K. A. Athanasiou GGN, C. M. Agrawal. Sterilization, toxicity, biocompatibility and clinical applications of polylactic acid/ polyglycolic acid copolymers. Biomaterials 1996;17:93-102.
32.Kohn DMSaJ. A synthetic polymer matrix for the delayed or pulsatlie release of water-soluble peptides. Control Release 2002;78:143-153.
33.B. Twaites CdlHAaCA. Synthetic polymers as drugs and therapeutics. Materials Chemistry 2005;15:441-455.
34.Anderson JM, Shive MS. Biodegradation and biocompatibility of PLA and PLGA microspheres. Advanced Drug Delivery Reviews 1997;28(1):5-24.
35.Uhrich KE. Polymeric Systems for Controlled Drug Release. Chem Rev 1999;99:3181-3198.
36.S. J. Huang DABaJRK. Biodegradable polymers: Chymotrypsin degradation of a low molecular weight poly(ester-urea) containing phenylalanine. Applied Polymer Science 1979;23:429-437.
37.Pitt CG. In Biodegradable Polymers as Drug Delivery Systems., 1990.
38.W. Lemn JK, G. Regier, K. Gerlach and E. S. Bucherl. Biodegradation of some biomaterials after subcutaneous implantation. Artif Organs 1981.
39.Gopferich A. Mechanisms of polymer degradation and erosion. Biomaterials 1996;17:103-114.
40.M. Dunne OICaRZ. Influence of particle size and dissolution conditions on the degradation properties of polylactide-co-glycolide particles. Biomaterials 2000;21:1659-1668.
41.M. L. T. Zweers GHME, D.W. Grijpma and J. Feijen. In vitro degradation of nanoparticles prepared from polymers based on DL-lactide, glycolide and poly(ethylene oxide). Controlled Release 2004;100:347-356.
42.Schliephake H, Klosa D, Rahlff M. Determination of the 3-D morphology of degradable biopolymer implants undergoing in vivo resorption. Biomedical Materials Research 1993;27:991-998.
43.S. R. Rajevv SM, G. P. Talwar. Biodegradable delivery system for single step immunization with tetanus toxoid. International journal of pharmaceutics 1993;93:R1-R5.
44.Alexis F. Factors affecting the degradation and drug-release mechanism of poly(lactic acid) and poly [(lactic acid)-co-(glycolic acid)]. Polymer International 2005;54:36-46.
45.N. Wang JSQaXSW. In Tailored Polymeric Materials for Controlled Delivery Systems. American Chemical Society Washington, DC 1998:242-254.
46.F. Alexis SKR, H. G. Leong and S.S. Venkatraman. In vitro study of release mechanisms of paclitaxel and rapamycin from drug-incorporated biodegradable stent matrices. Controlled Release 2004;98:67-74.
47.D. Cam SHHaYI. Degradation of high molecular weight poly( -lactide) in alkaline medium. Biomaterials 1995;16:833-843.
48.H. Pistner DRB, J. Mühling, J. F. Reuther. Poly(L-lactide): a long-term degradation study in vivo. Part III. Analytical characterization. Biomaterials 1993;14:291-298.
49.M. Vert SLaHG. More about the degradation of LA/GA-derived matrices in aqueous media. Controlled Release 1991;16:15-26.
50.K. Fu DWP, A. M. Klibanov and R. Langer. Visual evidence of acidic environment within degrading poly(lactic-co-glycolic acid)(PLGA) microspheres. Pharmaceutical Research 2000;17:100-106.
51.E. Cohen-Sela OR, J. Gao, H. Epstin, I. Gati, R. Reich, H.D. Danenberg and G. Golomb. Alendronate-loaded nanoparticles deplete monocytes and attenuate retenosis. Controlled Release 2006;113:23-30.
52.J. Siepmann NF, J. Akiki, J. Richard and J.P. Benoit. Effect of the size of biodegradable microparticles on drug release: experiment and theory. Controlled Release 2004;96:123-134.
53.C. E. Holy SMD, J. E. Davies and M. S. Shoichet. In vitro degradation of a novel poly (lactide-co-glycolide) 75/25 foam. Biomaterials 1999;20:1177-1185.
54.Wang XSWaN. Synthesis, characterization, biodegradation, and drug delivery application of biodegradable lactic/glycolic acid polymers. II. biodegradation. Biomater Science 2001;12:21-34.
55.A. Brunner KMaAG. pH and osmotic pressure inside biodegradable microspheres during erosion. Pharmaceutical Research 1999;16:847-853.
56.J. E. Bergsma WCdB, F. R. Rozema, R. R. M. Bos and G. Boering. Late degradation tissue response to poly(L-lactide) bone plates and screws. Biomaterials 1995;16:25-31.
57.A. C. R. Grayson MJC, R. Langer. Size and temperature effects on poly(lactic-co-glycolic acid) degradation and microreservoir device performance. Biomaterials 2005;26:2137-2145.
58.高振雄譯著. 電漿化學.
59.Boenig HV. Plasma Science and Technology. New York, 1982.
60.Evans BJBaPD. The Influence of Asperity Deformation Conditions on the Abrasive Wear of gamma –Irradiated Poly(Tetrafluoroethylene). Wear of Materials 1989;2:449-457.
61.Doban RC. Paper presented at 130th Meeting of the American Chemical Society. New Jersey 1956.
62.E. S. Clark LTM. Paper presented at 133nd Meeting of the American Chemical Society. New York, 1957.
63.I. K. Kang OHK, Y. M. Lee, and Y. K. Sung. Preparation and surface characterization of functional group-grafted and heparin-immobilized polyurethanes by plasma glow discharge . Biomaterials 1996;17:841-847.
64.Wu YLHaMP. Residual Reactivity for Surface Grafting of Acrylic Acid on Argon Glow-Discharged Poly (ethylene terephthalate) (PET) Films. Applied Polymer Science 1991;43:2067-2082.
65.Hansen RH. Effect of Atomic Oxygen on Polymers. Polymer Science 1965;3:2205-2214.
66.Turban MKaG. Mechanism of Etching and of Surface Modification of Polyimide in RF and LF SF6-O2 Discharges. Plasma Chemistry and Plasma Processing 1986;6:349-380.