可定位投遞藥物兩階段控制釋放微針陣列應用於黑色素沈澱之治療

Localized Two Steps Controlled Released Microneedle Patch for Transdermal Drug Delivery

黃資惠(TzuHui, HUANG)

指導教授 ： 傅建中 ； 宋信文

國立清華大學/工學院/奈米工程與微系統研究所/碩士(2013年)

https://doi.org/10.6843/NTHU.2013.00416

摘要

經皮藥物投遞系統 (transdermal delivery systems)是一種具備良好控制性、無疼痛感，且可專一性的投藥至皮膚組織的技術。本研究之目標是建立一個可針對特定深度的組織投藥且兩階段釋放之微針陣列，而本實驗利用黑色素沈澱之動物模型來研究微針陣列之療效。
黑色素沈澱是一種相當常見的皮膚症狀，特別是亞洲人、非洲人與南美洲人等。現今臨床治療上，有許多化學合成或者天然的藥物可治療黑色素沈澱，無論是單一配方或者是使用多種藥物的複方治療，皆有不同程度的療效與副作用。其中，治療黑色素沈澱之「三合一美白藥膏」，在許多的臨床實驗皆已證實其療效與安全性，然而，高達 87.5% 的使用者在治療過程中同時也會出現程度不等的副作用如患部脫皮、紅腫等現象。
為改善傳統三合一美白藥膏的療效，本研究提出兩階段給藥微針系統，針對黑色素沈澱的患部，施以兩階段溶解的微針貼片。第一階段快速溶解的微針針頭，將作用於黑色素細胞所在的基底層，抑制黑色素的生成；第二階段則是採緩慢溶解材料，將抑制發炎之類固醇置於微針底座部份，使其在角質層中緩慢溶解，達到緩釋給藥的效果。
本研究織成果顯示了已成功製備兩階段給藥微針系統，可將特定藥物成功定位於微針陣列之針尖，並於體外實驗中觀察到兩階段釋放之現象。本研究亦進行了動物實驗，證實了兩階段給藥微針系統確有治療黑色素沈澱之效果。而本系統所俱備的定位、兩階段投藥的優勢，預期也能在其他黑色素細胞相關病變（如黑色素瘤等）有臨床應用的潛力。

關鍵字

微針 ； 黑色素沈澱 ； 經皮傳輸

並列摘要

Hyperpigmentation is a hypermelanosis occurring in all skin types and results from the overproduction of melanin or an irregular dispersion of pigment after cutaneous inflammation. Patients with hyperpigmentation can have a significant psychosocial impact on skin-of-color patients, including Asian.
There are a variety of medications and procedures added to photoprotection cream that can safely and effectively treat hyperpigmentation. A fixed triple combination cream, containing 4% Hydroquinone (HQ), 0.05% Tretinoin (Vit. A acid), and 0.01% fluocinolone acetonide (steroids), called Tri-Luma from Galderma Laboratories (Fort Worth, TX), offer maximal efficacy for clinical trial. HQ and Vit. A Acid can inhibit the formation of melanin by inhibiting the tyrosinase in melanocytes in the bottom of epidermis layer. Fluocinolone acetone, the steroids can eliminate the irritation caused by hydroquinone or tretinoin. However, clinical study showed that over 87.5% of patients were noted to have side-effects with cream treatment because of the Hydroquinone cytotoxicity and slow degradation.
In this study, we proposed a new design of microneedles patch with different height for different skin layer to treat hyperpigmentation. For the deeper melanocyte in the bottom of epidermis layer, longer microneedle in the center of patch served as a fast released carrier loaded active ingredient HQ and Vit. A Acid for drug localization and fast metabolism to decrease HQ cytotoxicity. The shorter microneedle contained fluocinolone acetonide to dissolve gently in the keratinocytes layer to eliminate the irritation.
In vitro and in vivo study showed the feasibility of hyperpigmentation treatment. This approach could be a potential technology enabling direct transcutaneous delivery in clinical applications.

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