2013-01-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/651358摘要：我們團隊在過去幾年來致力發展用於腫瘤治療的「雙效微脂體Liposomal-Dox-Ce6」以及用於微生物感染治療之「chitosan光動力殺菌技術」。在腫瘤治療上我們結合了光動力治療與化學治療，光動力治療本身不但有殺死腫瘤細胞的效果，更進一步造成微脂體化療藥物釋放模式的改變，進而提高腫瘤化療的效果。而在感染性組織如傷口感染的治療上，幾丁聚醣(chitosan) 在光動力殺菌的協同作用，讓我們得以在低劑量光動力殺菌條件下，降低對正常組織細胞可能有的傷害，但同時提高殺菌的療效。由於光動力治療結合了不同藥物或生醫材料，進而在治療上發揮了協同效果，因此稱之為「雙療效光動力技術平台」。 為將光動力醫學更有效且實際應用於癌病變及抗藥性致病菌的治療，在這一個連續型計畫中，我們擬將「雙療效光動力技術平台」發展成能用於不同適應症的治療平台，以便在臨床上對更多腫瘤及感染性組織的治療提供新的方法。在現有第一年轉譯醫學研究計畫的支持下，我們發展出新療效之雙效微脂體Liposomal-Cisplatin-Ce6注射用劑型，並進行相關性質分析、in vitro的細胞實驗及初步in vivo動物實驗。而在光動力殺菌的研究上，我們以chitosan為原料，製成幾丁聚醣凝膠(chitosan gel)，並在現階段藉由光感物質TBO包埋，來進行相關性質分析並在生物膜上進行殺菌成效測試。 在接續下來兩年的研究計畫中，我們主要研究目的有四。第一、延續現有計畫中「雙療效光動力技術平台」的發展。將用於腫瘤治療的雙效微脂體（Liposomal-Cisplatin-Ce6）劑型和包埋有光感物質以做為感染性組織治療的chitosan 凝膠劑型，這兩個平台技術進行最適化研究。第二、完成這兩個光動力技術平台相關性質分析以及in vivo動物實驗，以為後續臨床測試而準備。第三、將能辨識腫瘤的 targeting peptides接上此雙效微脂體，以進一步建構出一種具active targeting能力之主動標的雙效微脂體，使之具備更專一性辨&#63996;腫瘤組織的能力。第四、將「Liposomal-Cisplatin-Ce6」及「含有TBO的幾丁聚醣凝膠」應用於獸醫犬腫瘤及微生物感染的治療。<br> Abstract: Previously, we have developed dual-effect liposome (Liposomal-Dox-Ce6) for the treatment of neoplasia. Meanwhile, we also found that the combination of PDI and chitosan has synergistic effect in eradicating microbial infections compared to PDI or chitosan alone. These studies indicate that a dual-effect PDT platform is quite promising for the management of neoplastic and infectious tissues. In this project, we intend to further develop this photodynamic technology platform into a dual-effect system which can be used for different clinical indications related to cancer and infectious diseases. Presently, we have sucessfully verified this dual-effect liposomal technology platform could be used to encapsulate different chemotherapeutical drug. The characteristics, in vitro cell culture and in vivo animal study of the Liposomal-Cisplatin-Ce6 are under investigation. Meanwhile, the chitosan gel containing TBO has been used to examine its antimicrobial efficacy by using biofilm. To fulfill the goals of developing this dual-effect PDT platform for the treatment of cancer and infectious diseases, four specific aims are proposed in the following two yeas. First, to optimize the dosage forms of Liposomal-Cisplatin-Ce6 and chitosan gel carrying TBO and to prove the efficacy of these two drug-delievry systems in vitro and in vivo; Second, to develop an active targeting dual-effect liposome and to prove the efficacy in vitro and in vivo; Third, to test the treatment efficacy of “Liposomal-Cisplatin-Ce6” and “chitosan/TBO gel” in the veterinarian dog with tumor or microbial infection;光動力治療微脂體化學治療腫瘤組織感染性組織Photodynamic therapyliposomechemotherapycancerinfectious disease