透過您的圖書館登入
IP:18.222.162.216
  • 學位論文

醣類高分子微針陣列之製作與細胞毒性測試及臨床前活體實驗

The polysaccharide microneedle fabrication, cytotoxicity analysis and animal test

指導教授 : 程耀毅
共同指導教授 : 華國媛(Kuo-Yuan Hwa)

摘要


傳統藥物輸送途徑:侵入性、經皮給藥與腸道交付療法中,受限於人體消化系統的特性、皮膚的保護與感覺神經的刺激等障礙,有著相當多的限制。針對經皮藥物輸送,與侵入式混合的微侵入法則就此萌發;其提高了藥物分子的運輸效率、減少不必要的疼痛與改進了傳統經皮藥物運輸療法的分子限制,成為新興的藥物輸送研究目標並展現了可能性。 基於傳統有機高分子鑄造微侵創微針陣列的製作方式,我們利用主流的低溫真空沉積微成型微針陣列鑄造法為基礎,提出了一種新的觀點針對繁瑣流程的缺點進行改善,並且提升了實驗的再現性。同時,利用一系列實驗設計的檢測環節,我們希望能驗證其設計發想對於微針陣列的研究與發展有正面的影響,而且保有對各色微針鑄造方法的相容性。以上述之微針為基礎,我們更進一步採用了活體的動物表皮穿刺,併用免疫染色法(IHC)檢測,對藥物輸送過程中侵入的深度與造成的侵入口的形狀等項目做出詳盡的報導,以此回饋實驗的設計,並獲得成品相關的驗證。

並列摘要


The tradition drug delivery systems: invasion, transdermal, oral, are limited by the protection of skin layers, response of the sensory receptors, chemical environment of the digestive system, and etc.. The Microneedle arrays (MNs) which combines the superiorities of systems form invasion and transdermal, shows a higher efficiency, capability of drug molecular and less pain. Based on these advantages, the MN techniques reveal a possibility for future researches. According the low temperature vacuum deposition micro-moulding methodology, we build a new optimization viewpoint for biodegradable polysaccharide MNs. In this study, a new workflow are designed to improve the manufacturing process and reach the goals: simplified steps of model fabrication, higher the production yields. With a series of check points for physical properties and animal experiments, we focus on physical properties to characterize materials and end products. These steps verify the compatibility with traditional casting techniques. Furthermore, the animal experiments which test for depth of skin puncture, drug diffusion under Immunohistochemistry (IHC), are planned to feedback the modification shape on model and progress in casting steps for prospect.

參考文獻


[3] James Le Fanu, The Rise And Fall Of Modern Medicine, Hachette UK, 2011, pp 3-4 (Google Digital Book Edition).
[9-10, 32] M. Gibaldi, R. N. Boyes and S. Feldman, “Influence of first-pass effect on availability of drugs on oral administration”, Journal of Pharmaceutical Sciences, Volume 60, Issue 9, 1971, pp 1338–1340; Article first published online in 2006.
[14-15, 30] Anna M. Wokovicha, Suneela Prodduturia, William H. Doub, Ajaz S. Hussain, Lucinda F. Buhse, “Transdermal drug delivery system (TDDS) adhesion as a critical safety, efficacy and quality attribute”, European Journal of Pharmaceutics and Biopharmaceutics, Volume 64, Issue 1, pp 1–8, 2006.
[16, 36] Jeffrey D. Zahn, Neil H. Talbot, Dorian Liepmann, Albert P. Pisano, “Microfabricated Polysilicon Microneedles for Minimally Invasive Biomedical Devices”, Biomedical Microdevices, Volume 2, Issue 4, pp 295-303, 2000.
[17-18, 21-28] Kathi C Madison, “Barrier Function of the Skin: "La Raison d'Etre" of the Epidermis”, Journal of Investigative Dermatology, Volume 121, 2003, pp 231–241

延伸閱讀