聚乳酸微針貼片製作與其帶藥之可行性評估

Microneedle Patches Made by Poly-Lactic Acid and the Assessment of Drug Loading Feasibility

蕭孟烜(Hsiao, Meng Hsuan)

指導教授 ： 劉大佼

國立清華大學/工學院/化學工程學系/碩士(2016年)

摘要

本研究目標為以聚乳酸 (poly(lactic acid), PLA)製作非水溶性高分子微針貼片，並搭配螢光染劑，分別以定量注藥及浸沾式塗佈方式探討藥物外塗於微針貼片之現象及定量藥物之可行性，以提供完整微針貼片之藥物傳輸平台。
本研究一共分為兩階段進行，第一階段為疏水性微針貼片之製作，包含配方、製程、檢測三個部分，第二階段則為微針搭配螢光染劑之帶藥探討。第一階段微針載具製作部分，本研究選用PLA混合丙酮之疏水性高分子塗液，分別製作兩種形態之微針，其一為室溫乾燥型微針，經由塗佈、真空抽氣、乾燥三大步驟製成微針貼片；另一熔融型微針為利用塗液抽真空搭配高溫熔融製程，抑或直接以顆粒熔融方式製作微針貼片。經由顯微鏡觀察微針表面結構、微針機械強度分析以及豬皮穿刺，以確認第一階段微針貼片品質之後，方可進行第二階段之螢光染劑藥物結合。
目前研究結果顯示，已可製作出品質良好之微貼片，至於外塗帶藥部分，首先在定體積注藥方面，我們發現在乾燥過程中，塗液將在微針間形成一半月形圖形，且其曲率半徑將在液體於微針表面形成一固定接觸點後，方開始有劇烈變化；而此過程中，雖然液體黏度越高，曲率半徑越小，且固定點所形成位置越高，然而表面張力會消弭掉黏度所造成之差異，為影響最終乾燥狀態之主要因子。而在浸沾式塗佈帶藥方面，我們建立一浸沾式塗佈系統，並搭配流場觀測攝影機，利用調控不同塗液特性及操作參數來了解帶藥過程。初步結果顯示其帶藥量與Ca值(=μV/σ)呈正相關，其中μ為液體黏度，V為塗佈拉升速度，σ為液體表面張力，而造成此結果之原因推測為拉升過程中，微針與液體間所形成之液體橋斷裂現象有關；另外我們也發現在乾燥時，塗液將會受重力影響而於微針表面形成一薄膜，然而因毛細現象影響，仍在努力解決如何精準控制每一根微針浸入高度，進而精準控制帶藥量。

關鍵字

非水溶性微針貼片 ； 浸沾式塗佈 ； 外塗帶藥 ； 流場觀測

並列摘要

The objective of this research is to fabricate a poly(lactic acid) hydrophobic microneedle (MN) patch and also to assess the feasibility of drug loading process with dropping and dip coating techniques.
This research is divided into two stages: fabrication of MN patches and the study of the drug loading process. The first stage includes three parts, i.e., formulation, experimental process and microneedle property test. We fabricated two different kinds of MN patches. The first one was based on PLA solution. The development included coating, vacuuming and drying under room temperature (RT). The other one is the melting type MN patches. We could either employ the high temperature melting process, or directly melt the PLA particles to obtain the patches. As soon as the fabrication process was completed, we then used digital camera to visualize the structure and configuration of the needles. Needle fracture force test and porcine skin penetration test were also applied to make sure the needle achieve the designated strength. When obtaining the acceptable MN patches, we then moved to the second stage - using the fluorescent drug test solution to study the drug loading process on the MNs.
The results indicate that we can successfully fabricate a high quality MN patch. As for drug loading, when dropping a designated volume of drug solution, we found the solution could form a meniscus shape between the needles, and there also existed a “pin point”, where the curvature would start to change dramatically. In this drying process, although higher viscosities would lead to higher curvature and pin point positions, liquid surface tension would mitigate the effect of viscosity, which was actually the dominant factor on the curvature of the meniscus. As for the study of dip coating, we established a dip coating system with a flow visualization apparatus. The preliminary results show that the drug loading amount is proportional to the capillary number (=μV/σ) where μ,V and σ represent liquid viscosity, coating velocity and fluid surface tension, respectively. During the drying process, gravity would pull the liquid flow downward and thus formed a thin film on the needle surface. However, due to the capillary effect, the prediction of the dipping length could be difficult.

並列關鍵字

hydrophobic MN patches ； dip coating ； drug coating ； flow visualization

參考文獻

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