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研究生: 陳凱翔
Chen, Kai-hsiang
論文名稱: 藉可降解高分子包覆以延長人工髖關節自我抗生素釋放時間
Prolong Antibiotics Release by Encapsulating PLGA for Hip Prosthesis
指導教授: 葉明龍
Yeh, Ming-long
賴國安
Lai, Kuo-an
學位類別: 碩士
Master
系所名稱: 工學院 - 醫學工程研究所
Institute of Biomedical Engineering
論文出版年: 2009
畢業學年度: 97
語文別: 英文
論文頁數: 64
中文關鍵詞: 深部感染聚乳酸-甘醇酸共聚合物抗生素人工髖關節
外文關鍵詞: antibiotics, Hip prosthesis, Deep infection, PLGA
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  • 全人工關節手術後引起的深部感染現在被認為是最具傷害性的併發症之一,深部感染患者必須承受數次手術及長時間的住院治療。
    此研究藉由包覆生物可降解性聚乳酸-甘醇酸共聚合物(PLGA)於塗佈有抗生素的人工髖關節鈦合金材料來避免抗生素突釋現象及延長抗生素自材料表面的釋放時間並且控制抗生素穩定釋放。研究中選用了兩種抗生素(Vancomycin及Cefuroxime),嘗試不同濃度及不同層數的聚乳酸-甘醇酸共聚合物包覆以期能發現較佳的抗生素釋放曲線。
    抗生素釋放情況藉由藥物沖出實驗得知,將金屬試片浸泡在磷酸鹽緩衝溶液(PBS)並利用旋轉器連續搖晃。在第1、6、12、24及每24小時收集PBS使用光譜儀分析抗生素濃度並更新PBS。抗生素的釋放與包覆的聚乳酸-甘醇酸共聚合物之降解有關。藉由量測沖出溶液的酸鹼度變化(pH值)、金屬試片重量變化及使用金相顯微鏡觀察表面型態來探討聚乳酸-甘醇酸共聚合物的降解情形。
    實驗結果顯示四組參數中:單層15%聚乳酸-甘醇酸共聚合物包覆Vancomycin、單層15%聚乳酸-甘醇酸共聚合物包覆Cefuroxime、雙層15%聚乳酸-甘醇酸共聚合物包覆Cefuroxime 及 第二層30%聚乳酸-甘醇酸共聚合物包覆第一層15%聚乳酸-甘醇酸共聚合物使用Cefuroxime 的組別,有效的抗生素釋放時間分別為5、7、10、17天。實驗結果顯示,在相同的聚乳酸-甘醇酸共聚合物包覆參數下,cefuroxime 相較於vamcomycin有較長的藥物釋放時間。實驗證實使用生物可降解性聚乳酸-甘醇酸共聚合物包覆抗生素可在體外的快速沖出實驗中延長抗生素釋放至少2.5個禮拜。在體內試驗或許能達到更長的釋放時間以達臨床應用要求。

    Deep infection after artificial joint arthroplasty is considered as one of the most devastating complications. Patients with deep infection may suffer from multiple surgeries and long period of hospitalization.
    In this study, encapsulating antibiotic loaded titanium alloy hip prosthesis materials by biodegradable poly(lactic-co-glycolic acid) copolymer (PLGA) were fabricated to extend period for steady antibiotic release and prevent burst antibiotic release. Two antibiotics (Vancomycin and Cefuroxime) and different concentrations and layers of PLGA encapsulations were investigated to find the optimal antibiotic release.
    The antibiotic release was quantified with elution test by immersed the samples in Phosphate buffer solution (PBS) then shaken with rotator. At 1, 6, 12, 24, and every 24 hours, extracts from eluting PBS were collected for antibiotic concentration analysis by spectrophotometer and replaced with fresh PBS. The antibiotic release was correlated with the degradation of PLGA. Weight change, pH value and metallographic microscopy were used to investigate PLGA degradation.
    The results shows the effective antibiotic release for single layer 15% PLGA on Vancomycin group, single layer 15% PLGA on Cefuroxime group, double layers 15% PLGA on Cefuroxime group, and one layer 30% over one layer 15% PLGA on were 5, 7, 10 and 17 days respectively. Cefuroxime has a longer drug releasing period than vancomycin in this PLGA encapsulating approach. In conclusion, this biodegradable PLGA encapsulating antibiotic strategy can extend antibiotic release up to 2.5 weeks in fast in vitro elution test. It could be further extended the release to longer time in vivo to reach the clinical effectiveness.

    中文摘要 I Abstract III 致謝 V Table of Contents VIII Table Contents X Figure Contents XI Chapter 1: Introduction 1 1.1 Arthroplasty 1 1.1.1 Arthroplasty Infection 2 1.1.2 Two-Stage Revision Surgery 3 1.2 Bacteria 4 1.2.1 Bacteria Growth and Reproduction 5 1.2.2 Bacterial Infection 7 1.2.3 Staphylococcus Aureus 8 1.2.4 Staphylococcus Epidermidis 10 1.3 Antibiotic 12 1.3.1 Vancomycin 13 1.3.2 Cefuroxime 15 1.3.3 Minimum Inhibitory Concentration 17 1.4 Biodegradable Materials 19 1.4.1 Biomedical Applications 20 1.4.2 PLGA: poly(lactic-co-glycolic acid) 20 1.5 Local drug delivery system 22 1.5.1 Biomedical Applications 23 1.6 Motivation and Purpose 23 Chapter 2: Materials and Methods 25 2.1 Antibiotic Loading 25 2.2 PLGA Encapsulating 26 2.3 Elution Test 27 2.4 Antibiotic Residual 27 2.5 Spectrophotometer 28 2.6 PLGA Degradation Rate 29 2.7 pH value 29 2.8 Metallographic Microscope 30 2.9 Anti-bacteria test 30 2.10 Data Analysis 34 2.11 Materials 35 2.12 Instruments 36 Chapter 3: Results 37 3.1 Encapsulated PLGA weight 37 3.2 Antibiotic Release 38 3.3 Antibiotic Residual 42 3.4 PLGA Degradation 43 3.5 pH Value 45 3.6 Surface Morphology 46 3.7 Anti-bacteria Test 47 Chapter 4: Discussions 50 4.1 Encapsulated PLGA Weight 50 4.2 Antibiotic Release 50 4.3 Antibiotic Residual 53 4.4 PLGA Degradation 53 4.5 pH Value 54 4.6 Surface Morphology 54 4.7 Anti-bacteria Test 55 4.8 Limitations 56 Chapter 5: Conclusions and Future Work 57 References 59

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