PMMA微針陣列的製備與其性質研究

Abstract

經皮給藥為現在非常常見的藥物傳輸方式，但在治療上經皮給藥還是受到非常多的限制，傳統上的經皮給藥只能夠傳輸小分子藥物或是親脂性藥物，大分子藥物及親水性的藥物皆會被皮膚最外層的角質層所阻擋。最近有一種可以增加皮膚滲透性的微米級針頭被提出並受到關注，利用微針進行藥物傳輸顯示出可以大大提高其傳輸量尤其是對於大分子藥物，微針現在已經廣泛應用於傳輸藥物、疫苗甚至DNA。使用微針與傳統針劑相比有非常多的優點，其一因為微針針頭大約長100~200μm，不會刺穿到真皮層接觸到神經故施打完畢後不會產生疼痛感；其二微針給藥不需要專業醫療人員協助即可自行施打;其三微針能夠結合貼劑穩定的進行長期給藥。 本研究是利用PDMS先將醫美用的微針模型進行翻模，之後利用兩階段注入PMMA的方式聚合形成PMMA微針陣列，微針幾何大小約為1cm*1cm的面積大小每一片微針陣列的個數為6*6的正方形陣列。利用細胞不喜歡貼附在PDMS材料上的特性將PDMS塗抹於cell culture底部，並將細胞與材料一起放入cell culture裡觀察其是否會成功貼附在PMMA微針陣列材料上。 由結果顯示利用兩階段的聚合方法聚合PMMA微針陣列是可行的，3T3細胞能成功得貼附在PMMA微針陣列上，在刺穿測試中發現PMMA微針陣列有與金屬微針陣列一樣的尖銳度、硬度能表現在刺穿去細胞化的豬皮表層上，在耐力測試中發現刺壓10次去細胞化的豬皮表層後PMMA微針陣列針尖會開始產生斷裂的情形而刺壓到50次之後PMMA微針陣列的針尖會全部斷裂，故PMMA微針陣列刺壓50次可能是一個極限，在細胞毒性的測試下發現聚合完全的PMMA是不會對細胞造成傷害或毒性。

Transdermal administration is a very common drug delivery route currently, but it encounters a lot of restrictions. Traditionally, transdermal administration only transfers small molecule drugs or lipophilic drugs, due to the fact that macromolecular drugs and hydrophilic drugs might be blocked by the skin’s stratum corneum. Micro-scale needles have been proposed and notified to increase skin permeability recently. This micro-scale needles called microneedles. Using this microneedle array, transdermal drug delivery shows to greatly enhance the skin permeation capacity especially for macromolecular drugs. Microneedle array is widely used in drug delivery, vaccine even DNA delivery through skin. Microneedle array has a lot of advantages as compared with conventional injection. First, microneedle’s length is about 100 ~ 200μm, which reduces the risk of the needles piercing into the dermis exposed to nerve and avoids the pains during the application on the skin. Second, microneedle administration is a self-medication and does not require the assistance from professional medical personnel. Third, microneedle array can be combined with the patch as a long-term method of administration. Using a two-stage injection, polymerization process polymeric polymethylmethacrylate (PMMA) microneedle array was formed success fully. The geometry size of PMMA microneedle array is about 1cm by 1cm. Each array of microneedle number is 6 by 6. We oberved whether the cell could be successfully attached to our material 'PMMA microneedle array.' The results show that two-stage polymerization process utilizing PMMA was feasible to produce microneedles. 3T3 cells successfully attached to the PMMA microneedle array. PMMA microneedle and metal microneedle were observed to have the similar hardness and sharpness, based on the outcomes obtained from piercing through the decellularized pigskin. In endurance tests, following ten times application of PMMA microneedle array on the decellularized pigskin, PMMA microneedle array would begin to break. After fifty times of application, PMMA microneedle array would all be broken. Under cytotoxicity tests, completely polymerized PMMA did not cause injury or toxicity to cells.