含鐵有機金屬框架結合具生物相容性之微針系統於局部經皮應用

Abstract

皮膚纖維化是由於正常的傷口修復機制失調，導致過度膠原蛋白生成並形成異常疤痕。本研究提出一種具生物相容性的經皮藥物傳輸系統，將含鐵之有機金屬框架材料（MIL-100(Fe)）結合於可溶性微針貼片中，並選用聚乙烯醇（PVA）或羧甲基纖維素鈉（CMC）作為基材。MIL-100(Fe)藉由微波輔助水熱法合成，並透過X光繞射（XRD）、掃描式電子顯微鏡（SEM）、穿透式電子顯微鏡（TEM）、氮氣吸附脫附測試與動態光散射（DLS）等技術進行結構與物性分析，結果證實其具備良好的結構完整性、形貌均勻性與穩定性。細胞毒性測試顯示，MIL-100(Fe)對人類蟹足腫纖維母細胞在最高至500 μg/mL的濃度下仍保有90%以上的細胞存活率，展現出優異的生物相容性。機械性質分析指出，7 wt%的CMC擁有較7 wt%的PVA更高的楊氏模數，但兩者皆需進一步優化以達成理想的皮膚穿透能力。豬皮體外實驗顯示，相較於固定力插入，施加瞬間手部壓力能有效提升微針穿透效果。綜合而言，本研究所開發之MIL-100(Fe)載藥微針系統具備局部、微創治療皮膚纖維化的潛力，未來可透過微針結構與材料成分的調整進一步優化其治療效果。

Skin fibrosis arises when normal wound repair becomes dysregulated, leading to excessive collagen production and the formation of abnormal scars. This study proposes a biocompatible transdermal delivery system that incorporates iron-based metal-organic frameworks (i.e., MIL-100(Fe)) into dissolvable microneedle patches made from polyvinyl alcohol (PVA) or sodium carboxymethyl cellulose (CMC). MIL-100(Fe) was synthesized through a microwave-assisted hydrothermal method, and it was characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), N2 adsorption/desorption, and dynamic light scattering (DLS) analyses. These characterizations confirmed its structure, uniform morphology, and good colloidal stability. Cytotoxicity tests conducted on human keloid fibroblasts indicated high cell viability of over 90% at concentrations up to 500 μg/mL, demonstrating excellent biocompatibility. Mechanical analysis showed that 7 wt% CMC exhibited a higher Young’s modulus than 7 wt% PVA. However, both polymers will require further optimization to ensure complete skin penetration. In vitro tests on porcine skin revealed that applying microneedles with manual pressure resulted in better insertion compared to a constant-force application. Overall, the MIL-100(Fe)-loaded microneedle system offers a promising strategy for the localized, minimally invasive treatment of skin fibrosis, with potential for further refinement in both structure and composition.