溫度敏感型聚酯類水膠作為免疫抑制藥物傳遞系統之應用於同種異體皮膚移植

Thermosensitive Polyester Hydrogel for Application of Immunosuppressive Drug Delivery System in Skin Allograft

吳逸恩(I-En Wu)

指導教授 ： 朱一民 ； 陳韻晶

國立清華大學/工學院/化學工程學系/碩士(2022年)

摘要

他克莫司是一種的免疫抑制藥物，能夠用於抑制急性排斥反應，常用於同種異體移植後患者之治療，在血清中維持穩定的藥物濃度，會有比較良好的治療效果。然而，傳統的治療是利用口服或注射的途徑給藥，後者造成患者的不方便，前者會遇到藥物過量或患者在治療中依從性低下的問題。本研究選用溫度敏感型聚酯類水膠作為藥物載體，包覆疏水性免疫抑制藥物他克莫司，期望能藉由藥物控制釋放系統，達到緩慢且持續釋放的效果。材料的製備是以methoxy poly(ethylene glycol)作為起始劑，與D,L-lactide、caprolactone進行開環聚合反應，合成出mPEG-PLCL兩團聯共聚物，將這此種共聚物分別配製成水膠，比較不同組成水膠性質與包覆效果，以找出較適合包覆他克莫司之藥物載體。
其中，在本研究中我們嘗試不同的助溶劑以包覆他克莫司於mPEG-PLCL，最終發現以0.5 % 的PVP在藥物釋放以及包覆效果有最佳的效果。在體外藥物釋放以及動物實驗中，我們可以成功的讓藥物定點的穩定釋放30天也不會出現藥物突釋的現象。此外，從動物同種異體皮膚移植的實驗中，此劑型提高了移植的存活率。顯示出本研究的水膠配方具有傳送抑制免疫藥物，改善治療效果的潛力。

關鍵字

溫度敏感型 ； 他克莫司 ； 同種異體移植

並列摘要

Tacrolimus (FK506) is a common immunosuppressive drug that is capable of suppressing acute rejection reactions, and is used to treat patients after allotransplantation. A stable and suitable serum concentration of tacrolimus is desirable for better therapeutic effects. However, daily drug administration via oral or injection routes is quite inconvenient and may encounter drug overdose or low patient compliance problems. In this research, our objective was to develop an extended delivery system using a thermosensitive hydrogel of poly ethylene glycol, D,L-lactide (L), and ϵ-caprolactone (CL) block copolymer, mPEG-PLCL, as a drug depot. The formulation of mPEG-PLCL and 0.5% PVP-dissolved tacrolimus was studied and the optimal formulation was obtained. The in vivo data showed that in situ gelling is achieved, a stable and sustained release of the drug within 30 days can be maintained, and the hydrogel was majorly degraded in that period. Moreover, improved allograft survival was achieved. Together, these data imply the potential of the current formulation for immunosuppressive treatments.

並列關鍵字

thermosensitive ； tacrolimus ； allotransplantation

參考文獻

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