微針貼片是一種結合針劑注射與傳統經皮貼片優點之無痛式微侵入型醫療裝置，其微米級針狀結構可在不刺激末梢神經的情況下刺穿皮膚角質層，有效地將藥物傳送至皮膚深層。本研究將水溶性生醫高分子聚乙烯醇(polyvinyl alcohol, PVA)與聚乙烯吡咯烷酮(polyvinyl pyrrolidone, PVP)混合，經由兩階段離心灌模製程包覆美白活性成分傳明酸(tranexamic acid, TA)與維生素C棕櫚酯磷酸三鈉鹽(trisodium ascorbyl 6-palmitate 2-phosphate, APPS)，開發出一藥物集中於針尖之快溶型高分子美白微針貼片。研究中以等比例混合之PVP/PVA溶液製備出金字塔柱型高分子微針，配合自行研發之微針貼片貼敷器提供穩定的穿刺力道，由體外豬皮與活體天竺鼠穿刺測試證實此微針貼片具有足夠之機械強度可刺穿皮膚達150-200 m，附加之注水功能可幫助微針於穿刺後三分鐘內溶解並釋放藥物，透過多光子共軛焦顯微影像系統證實微針可傳輸藥物至約300 m的深度。此外，由高效液相層析(HPLC)定量結果證實，透過微針總體積與理論包藥量之計算，經兩階段離心灌模製程，可得到與理論值相近(準確度達90%以上)之實際包藥量。由細胞毒性試驗證實，高分子微針與各活性成分在35 g/ml 、70 g/ml與140 g/ml 三種濃度下皆不會對小鼠黑色素瘤細胞(B16-F10)造成強烈毒性。由儲存穩定性分析證實，美白微針貼片存放於40 C下一個月，仍可保持其化學結構穩定性。以棕色天竺鼠為動物模型，經照射UVB誘導天竺鼠皮膚黑色素沉著化，進行美白微針貼片之活體美白效力試驗，由結果推測，徒手按壓穿刺造成穿刺深度不足、穿刺頻率過於密集與天竺鼠過度誘黑(ΔL* ~ 20)三個原因，皆可能造成美白效果不明顯，未來將採用較長之微針結構、降低穿刺頻率與適度誘黑天竺鼠(ΔL* ~ 10)來改善美白效果。

Microneedle (MN) patches, combining the advantages of hypodermic needles and transdermal patches, have been proposed as a new tool for transdermal drug delivery, because of their efficient delivery and lack of pain. This study reports dissolving microneedles, composed of polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA), for rapid and efficient delivery of depigmentation agents, tranexamic acid (TA) and trisodium ascorbyl 6-palmitate 2-phosphate (APPS). We used a two-step casting process to localize agents in the tip of the needles and reduce drug wastage in the patch. The skin insertion tests showed that the developed microneedles were strong enough to insert into the epidermis layer (~150 m) of porcine cadaver skin and guinea pig skin using a homemade applicator. The designed applicator not only gives a predefined force for insertion, but also provides water to accelerate the microneedle dissolution during insertion. At 3 min post-application, the drug can be completely released from the dissolved microneedles and drug diffusion depth observed in the skin was approximately 300 m. Drug loading assay showed that the amount of drug loading is close to the estimated value obtained from calculation with an accuracy of ~90%. The cell study showed that the agents with the concentration of 35 g/ml, 70 g/ml and 140 g/ml have no cytotoxicity in B16-F10 mouse melanoma cells. Storage stability analysis confirms that the encapsulated agents retain their stability after storage at 40 C for a month. A brownish guinea pig model was used to evaluate the feasibility of using these dissolving microneedles to inhibit UVB-induced skin pigmentation. We found that insertion method, frequency and pigmentation extent may play key roles in the efficacy of skin depigmentation. We will find the optimal regimen to treat hypermelanosis using dissolving microneedles.

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