隨著世界癌症病例逐年上升，阿黴素作為抗癌藥物有良好的效用，但其副作用、快速降解、親水等特性限制其臨床上的使用，希望設計藥物載體以解決本問題。本實驗使用雙乳化法製作微球包覆阿黴素配合水膠方式與混合水膠方式觀察阿黴素藥物釋放情形，微球材料方面使用生物可降解型材料(poly(lactic-co-glycolic acid),PLGA)，水膠材料方面使用市售水膠F-127與本實驗室合成的水膠(Poloxamer-p(Ala)-p(Lys),PLXAL)。
水膠合成經由FTIR與氫核磁共振光譜鑑定成功合成出高分子水膠(PLXAL)，經由倒置法證明5wt%下能穩定在37℃成膠，顯示水膠低成膠濃度特性。降解實驗中PLXAL展現了高度穩定性與不易降解性，而F-127則具有快速降解特性，在PLXAL中參雜入水膠F-127發現結果會影響加速水膠降解速率，顯示混合水膠可做為一種調控降解速率方式。利用掃描式電子顯微鏡發現高分子水膠為依序排列片狀並具有三維網狀結構，加入水膠F-127後仍保有部分片狀結構，高分子微球部分，微球材料表面具有表面缺陷，隨著時間降解表面缺陷會越來越明顯，最後崩解出現的多孔洞結構證實有足夠空間包覆阿黴素，使用光學顯微計算微球粒徑，微球粒徑會隨著界面活性劑濃度而改變(60-80微米)。
藥物包覆率方面，水膠的包覆率皆在98%以上，微球方面T包覆率會隨著介面活性劑濃度與藥物投放量而變，經實驗參數的調整後，對於藥物阿黴素包覆率達到13.7%，說明以雙乳化法製作高分子微球具有包覆親水藥物能力。生物相容性實驗中，水膠微球與水膠系統都顯示高生物相容性。藥物釋放實驗中，實驗結果證實水膠包覆微球系統下有更佳緩釋效果、避免突釋的能力，而混合水膠表現出更快速的釋放速率與更高的釋放率，顯示混合水膠可為一種調控釋放方式。

The global epidemic of cancer is constant increasing. Doxorubicin is a widely used as chemotherapy agent. Despite its utility, several side effects were induced, especially its irreversible cardiotoxicity and nephrotoxicity, limiting its clinic application. To solve this issue, we used double emulsion method to prepare doxorubicin-loaded microspheres in hydrogel system. The microspheres were prepared by biodegradable materials. Hydrogels were hydrogel F-127 and polypeptide hydrogel Poloxamer-p(Ala)-p(Lys).
The characteristic of final synthetic production was examined by H-NMR, FT-IR and GPC. It showed that the copolymer PLXAL was successfully synthesized. By test-tube inversion method, P-PLX-Ala-Lys formed hydrogel at 37℃ with low concentration 5wt%. Furthermore, in vitro degradation test, PLXAL showed high stability and low-degradability; on the contrary, hydrogel F-127 group showed its easily degradable characteristics. We found that the mixed hydrogel system (5wt%PLXAL：3wt%F-127) would affect the degradation rate of hydrogel. The SEM micrograph indicated that these hydrogels arranged in a fibrous cross-linked structure and microspheres had defect on the surface in the beginning. As the collapse of microspheres, we observed that microspheres had porous structure, which made these microspheres to be as drug carriers. In the following, the particle size of microspheres was determined by OM. We found that the particle size was changeable from 60 to 80 micrometers depended on different concentrations of surfactant (PVA).
After that, the Encapsulation Efficiency (EE) and the Drug Loading (DL) were evaluated. In encapsulation test, the EE of hydrogels were approximately 98%. The EE and DL of microspheres were depended on the concentration of surfactant and the amount of loading-drug. After adjustment, EE of microspheres up to 13%. These results demonstrated that microspheres had the potential of hydrophilic drug encapsulation. In additional, hydrogels and microspheres showed their excellent biocompatibility. In vitro drug release experiment, drug release rates in hydrogels and microspheres in hydrogel system were measured for two weeks. No burst release happened in microspheres system and had better prolonged release than hydrogel systems. In terms of mixed hydrogel, the release rates were higher than PLXAL hydrogel. In summary, microspheres with hydrogel had stable drug release, compare with higher release rate of mixed hydrogel.Both of them can reach specific requirement for different application for drug delivery system.

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