複合性異體移植的病患常常因為免疫排斥導致移植物壽命縮短甚至失去功能，因此常常必須在手術後數年內使用免疫抑制劑他克莫司來降低排斥反應。而他克莫司目前臨床多使用每天注射及口服方式給藥。本研究透過新型溫度敏感型高分子PLX-b-poly(ʟ-alanine-lysine) (P-Lys-Ala-PLX)作為包覆他克莫司的長效型藥物緩釋水膠，期望能達到良好的藥物釋放效果，彌補臨床需求。
本研究透過1H核磁共振確認成功合成P-Lys-Ala-PLX共聚物，並藉由穿透式電子顯微鏡、動態光散射儀、掃描式電子顯微鏡、全反射傅立葉轉換紅外線光譜儀、流變儀等儀器觀測此溫度敏感型胺基酸水膠成膠機制，成膠後性質及胺基酸二級結構變化。實驗結果顯示4-5% P-Lys-Ala-PLX確實能夠在常溫為液態而體溫狀態形成膠體，並隨著溫度上升α-helix比例有增加趨勢。再者，透過改良水膠藥物載體配方，利用混摻少量pluronic F-127加速藥物釋放，此一複合劑型以高效能液相層析儀分析確認其配方能夠有效包覆藥物並達到緩慢長效釋放。研究成果顯示此材料及藥物載體配方具有相當潛力作為包覆免疫抑制劑的長效釋放劑型。

Tacrolimus is an immunosuppressive agent which is usually applied to patients who received allotransplantation to reduce immune rejection. The strong hydrophobicity of tacrolimus makes it difficult to be applied in aqueous system. It has been studied to be encapsulated by micelles. However, the low efficiency of encapsulation in micelles is an obstacle for further application. Polypeptide thermosensitive hydrogel is considered as a great candidate for drug delivery because of several advantages, such as excellent biocompatibility and biodegradability, low concentration for gelation and sensitive response temperature change. In this study, we synthesized a thermosensitive polypeptide hydrogel by copolymerizing poloxamer and poly(ʟ-alanine) with ʟ-lysine segments at the both ends to form PLX-b-poly(ʟ-alanine-lysine) (P-Lys-Ala-PLX) copolymers. Poly(ʟ-alanine) is the hydrophobic chain of P-Lys-Ala-PLX copolymers which was designed to capture the hydrophobic agents. The synthesis was examined by 1H NMR and showed that P-Lys-Ala-PLX copolymers was successfully synthesized. P-Lys-Ala-PLX has a sol-gel behavior with low concentration of 3-7 wt%. The formulation of mix hydrogel by mixing a little pluronic F127 showed high drug encapsulation efficiency. The experiment of drug release also showed that the tacrolimus released constantly over time. This study indicates that this copolymer and mix hydrogel formulation is a high potential injectable drug carrier for biomedical application.

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