本論文乃研發一鑲嵌式緩釋荷爾蒙新型微針系統，將生物可降解之幾丁聚醣(chitosan, CS)微針與水溶性聚乙烯吡咯烷酮(polyvinylpyrrolidone, PVP)和聚乙烯醇(polyvinyl alcohol, PVA)支撐陣列組合。此微針能在穿刺皮膚後，藉由體內組織液將後端支撐陣列溶解，僅留幾丁聚醣針體於皮膚中，緩慢而持續地釋放荷爾蒙；為改善本實驗室前一代幾丁聚醣微針在製程中大量損耗藥物之問題，本研究對製程進行改良，使割除之含藥幾丁聚醣貼片可回收再利用，達到100%藥物可利用率。由體外豬皮及體內大鼠穿刺試驗證實，所製備之微針皆具有足夠之機械強度可刺穿角質層，並讓微針鑲嵌於真皮層上方，深度約750微米。以標的螢光之牛血清蛋白作為model drug進行體外藥物釋放實驗，第七天時僅釋放約16%的藥量，證實幾丁聚醣微針可緩釋蛋白質藥物至少達七天以上。體內降解與釋放實驗亦證實，微針可於皮膚內逐漸降解並釋放藥物長達28天。將黃體激素釋放激素(luteinizing hormone-releasing hormone, LHRH)包覆於微針中，並儲存於室溫下一個月，經圓二色光譜儀證實其二級結構並無明顯改變。然而，人類生長賀爾蒙(human growth hormone, hGH)之二級結構卻有明顯地改變，將包覆hGH之微針應用於大鼠，僅能於第一天偵測到血中荷爾蒙含量，推測是因hGH在微針包覆過程中已造成蛋白質結構上的改變，進而影響其活性。未來將探討由幾丁聚醣微針釋放之LHRH之生物活性，評估其臨床應用之可行性。

This study introduces a microneedle system, composed of embeddable chitosan microneedles with a dissolvable poly(vinyl pyrrolidone)/poly(vinyl alcohol) (PVP/PVA) supporting array, for complete and sustained delivery of encapsulated hormone to the skin. In vitro and in vivo skin insertion test demonstrated that the obtained microneedles can penetrate through the stratum corneum. In vivo degradation and drug release study also confirmed that chitosan microneedles gradually degraded in the skin and provided a sustained release of BSA for at least 28 days.This results suggest that chitosan microneedles are a promising depot for sustained delivery for protein.

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