搭載薑黃素之藻酸鹽PLGA複合水膠敷料於糖尿病傷口治療上的應用

Abstract

傷口癒合障礙是糖尿病患者最主要的死因。它是多種因素引發的病症，涉及到一系列內皮細胞功能障礙、糖尿病性神經病變、抵抗感染的能力受損等因素。目前臨床上主要是通過抗氧化劑，針對內皮的修復機制進行治療。但單靠傳統的抗氧化療法無法完全解決多種因素引起的糖尿病傷口癒合障礙。由於神經病變在糖尿病模型中至關重要，因此我們猜想是否能通過神經與內皮並行治療的策略，為糖尿病傷口提供一種新的治療可能。本研究選擇對神經保護與修復、血管再生均有益處的薑黃素，搭載於PLGA上形成藥物控制釋放體系，並結合水膠以形成複合型的藥物遞送系統，製成傷口敷料。期待能增強糖尿病傷口局部的抗氧化、抗炎症能力的同時，關注神經保護部分，達到早期治療的功效。 本研究合成出平均粒徑，凍乾前為190 nm，凍乾後為416 nm，但凍乾後粒徑分布更集中。薑黃素於PLGA上搭載率為10 ± 0.07 %。於體外試驗中，複合型水膠敷料能維持5天的完整性，同時顯現出藥物緩釋的能力並仍具有抗氧化性；於纖維母細胞、帶有神經脊細胞性質的嗜鉻細胞瘤細胞試驗中，均表現出無毒性，且能有效加速細胞爬行，具有促進生長的功效。於動物實驗中，搭載有薑黃素的水膠敷料在大鼠上表現出更佳的癒合能力。本研究證實了薑黃素水膠在糖尿病傷口模型中具有早期治療的潛力。

Impaired wound healing is the major causes of death in diabetic patients. It is involved endothelial cell dysfunction, diabetic neuropathy and increased risk of infection. At present, the main clinical treatment is antioxidants, aiming at the repair mechanism of the endothelium. However, there is no single therapy to date can fully treat diabetes-induced wound caused by multiple mechanisms. A strategy of parallel treatment between nerves and endothelium may provide a new therapeutic possibility for diabetic wounds. In this study, curcumin was used due to its antioxidant, anti-inflammatory, antibacterial properties. PLGA loaded with curcumin as a drug controlled-release system, combined with sodium alginate were made for wound dressings. The average particle size was 190 nm and 416 nm, before and after freeze-drying, but polydispersity index decreased to 0.005. The loading rate of curcumin on PLGA was 10 ± 0.07 %. In vitro analysis, the dressings maintained for 5 days and showed the ability of sustained drug release, still with antioxidant; biocompatibility tests showed no toxicity on fibroblasts and PC-12. It accelerated cell crawling effectively. In vivo analysis, dressings loaded with curcumin showed better healing ability. This study confirmed the early therapeutic potential of curcumin hydrogel in a diabetic wound model.