雷奈酸鍶與聚乙烯亞胺-聚吡咯奈米顆粒結合甲基纖維素水凝膠局部應用於類風濕性關節炎動物模型

The local application of Strontium Ranelate with Methylcellulose hydrogel and Polyethylenimine-Polypyrrole nanoparticle on Rheumatoid arthritis of animal model

姜智偉(Chih-wei Chiang)

指導教授 ： 趙坤茂

國立臺灣大學/電機資訊學院/生醫電子與資訊學研究所/博士(2021年)

https://doi.org/10.6342/NTU202101818

摘要

本研究目的是探索光熱效應下所產生相互作用的多孔結構聚合物水凝膠對類風溼性關節炎(Rheumatoid arthritis, RA)的影響。類風溼性關節炎為自體免疫疾病，主要致病機轉是自體免疫系統主動攻擊身上的關節滑膜進而造成關節傷害。雷奈酸鍶(Strontiun ranelate, SrR)是一種口服抗骨質疏鬆藥物，具有雙重生物效果可以抑制骨吸收並促進骨生成。當雷奈酸鍶被製作成奈米化，可以增加表面積並提高吸收效率。聚乙烯亞胺聚吡咯(Polyethylenimine-Polypyrrole, PEI-PPY)聚合物具有光熱效應特性，在近紅外線 (Near Infra-red, NIR)刺激下可以產生熱能。新型非侵入性近紅外線具有優良的光熱轉換效應，可以利用熱能改變水膠物理及化學特性，此將協助奈米藥物在體內細胞間的移動，除此之外，熱能也會刺激局部血液循環協助將局部發炎物移除。文獻指出口服雷奈酸鍶不只可以抑制類風濕性關節炎症狀。口服雷奈酸鍶亦可以減緩退化性關節炎症狀。在此項研究中，我們製作具有光熱效應的雷奈酸鍶奈米粒子，包覆在新型態光熱溫感性水膠以利於局部應用於類風溼性關節炎治療。首先我們先以多種檢測方式測量此水膠聚合物的物理化學特性，並分別於體內及體外證實此水膠聚合物具有抗發炎作用。此外，我們再利用大鼠作先驅式類風溼性關節炎動物實驗，證實此水膠聚合物可以有效抑制類風溼性關節炎於大鼠膝關節，並為可吸收生物相容性無生物毒性聚合物。我們期望透過此研究可以開發出新型生物相容性水膠的應用於未來類風溼性關節炎治療方式。

關鍵字

類風溼性關節炎 ； 雷奈酸鍶 ； 光熱效應 ； 甲基纖維素 ； 聚乙烯亞胺聚吡咯奈米粒子

並列摘要

The purpose of this study is to explore the effect of the interaction of porous structure polymer hydrogels on rheumatoid arthritis under the photothermal reaction. Rheumatoid arthritis is an autoimmune disease. The main pathogenic mechanism is that the autoimmune system actively attacks the synovial membrane to result in joint destruction. Strontium ranelate (SrR) is an oral anti-osteoporosis drug. SrR have specific dual biological effects which inhibits bone resorption and promotes bone formation. When SrR is made into nanometer, it increases whole surface area which can improve absorption efficiency. Polyethylenimine-Polypyrrole (PEI-PPY) complex has characteristic of photothermal effect. Under the stimulation of near infra-red, PEI-PPY can release heat energy. The novel non-invasive near infrared (NIR) has an excellent photothermal conversion effect, which can produce heat energy to change the physical and chemical properties of the hydrogel. This photothermal effect will also assist the migration of nano-drugs into the host cell. Besides, the heat from photothermal reaction from NIR can also stimulate local blood circulation and help to remove products from local inflammation. Previous literature points out that oral SrR can not only suppress the symptoms of rheumatoid arthritis, it can also alleviate the symptoms of degenerative arthritis. In this study, we produced SrR nanoparticles with photothermal effect, and coated them in a new type of thermo sensitive hydrogel to facilitate local application in the treatment of rheumatoid arthritis. First, we first measured the physicochemical properties of the hydrogel polymer by a variety of detection methods. And we confirmed that the hydrogel polymer has anti-inflammatory effects in vivo and in vitro. We used rats as a pioneering animal model on rheumatoid arthritis, and confirmed that this hydrogel polymer can effectively inhibit rheumatoid arthritis in the knee joints of rats. This novel polymer is an absorbable biocompatible polymer without biological toxicity. We hope a new type of biocompatible hydrogel can be developed for future treatment of rheumatoid arthritis through this research.

並列關鍵字

rheumatoid arthritis ； strontium ranelate ； photothermal effect ； methylcellulose ； Polyethylenimine-Polypyrrole

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