具熱敏感性，生物可分解性，可注射性高分子作為喜樹鹼載體之研究

Abstract

本篇研究中，我們利用一種生物可分解性的單體（ε-Caprolactone）去和另一個生物可分解的高分子( polyehylene glycol）接合來製造高分子(PCL-PEG-PCL)。當高分子依照特定的單體重量比合成之後，其具有溫度敏感性並且可以水溶液的狀態下，隨著溫度作溶液和膠體間的相態轉變。由這種高分子所形成的膠體具有良好的生物可分解性及生物相容性。我們使用凝膠滲透層析儀和核磁共振來確認高分子的結構和分子量。然後使用熱重分析儀來測試其熱穩定性。我們在不同高分子濃度的溶液中混入化療藥物CPT-11和SN-38， 然後使用掃描式電子顯微鏡觀察這些膠體的結構。含有親水性藥物CPT-11的膠體型態會隨著高分子濃度的改變而改變。而同比例含有疏水性藥物SN-38的膠體型態則和含有親水性藥物CPT-11完全不一樣。在體外藥物釋放測試中，含有CPT-11的溫度敏感性水膠在高藥物濃度(5mg/ml)下，藥物在兩天內就完全釋放出來，而在同樣藥物濃度下，含有SN-38的水膠則在呈現出另外一種藥物釋放曲線，藥物在10天內穩定且緩慢的線性釋放。在動物實驗中，注射含有高濃度CPT-11水膠的實驗組和分五次低濃度注射以達到相同藥量的對照組，呈現出較低的毒性和相同的治療效果。而在注射含有高濃度SN-38水膠的實驗組，也呈現現出比對照組更低的毒性。因此，用這種具有溫度敏感性的水膠包覆化療藥物（CPT-11或SN-38）來作為一個原處釋放藥物的載體是非常合適的。

In this study, we use a biodegradable monomer (ε-Caprolactone) to combine with a biodegradable polymer (polyehylene glycol) and a biodegradable triblock copolymer (PCL-PEG-PCL) was synthesis. The triblock copolymer (PCL–PEG–PCL) is thermosensitive when weights of those monomers were combined at some special ratio and its aqueous solution can undergo the sol–gel–sol transition as the temperature increases. The hydrogel was fully biodegradable and biocompatible. GPC and NMR 1H are used for characterizing the polymer. Thermal stability was tested by TGA. Chemotherapy drugs：CPT-11 and SN-38 were loaded into hydrogel made by triblock copolymers at several concentrations. Then, a scanning electron microscope was used to observe morphology of hydrgel loaded with chemotherapy drugs. The morphology of hydrogel loaded with hydrophilic drug CPT-11 is different from the polymer concentrations and hydrogel loaded with hydrophobic drug SN-38 show another appearance under the same polymer concentration with CPT-11. In vitro drug release from thermosensitive hydrogel was investigated. CPT-11 was released within two days from hydrgel when they are loaded at a high concentration (5mg/ml). The releasing curve of hydrogel loaded with SN-38 at the same concentration shows a slowly stable and linear trend within 10 days. In vivo experiments of CPT-11 indicated that the treatment using hydrogel loaded with 5 doses (inject once) for suppressing tumor growth is the same effective as five injections and the toxicity is lower. In the experiments of SN-38, hydrogel loaded with 5 doses also shows a lower toxicity than five injections. Thus, they can be used as a suitable drug - polymer implant for local release of chemotherapeutic drug like irinotecan or SN-38.