傷口癒合是慢性疾病所面臨的主要議題之一，目前對於傷口癒合的治療方法效果普遍不佳，並容易產生副作用，而且價格昂貴。若能開發具有降低成本效益、來源天然且具生物降解的傷口敷料，以減少氧化、發炎和預防細菌感染對傷口癒合帶來的影響，對醫療體系而言將會是一大福音，而這樣的議題目前正被科學家們廣泛的研究。薑黃素有很多的治療用途，如抗氧化、抗菌和抗發炎活性，然而其低溶解度卻限制了薑黃素的臨床應用。在本研究中，薑黃素奈米粒子(Cur NPs)和薑黃素-幾丁聚醣奈米粒子(Cur-Chi NPs)被摻入膠原蛋白-香草醛(Van-Col)支架中，經用冷凍乾燥法來製備兩種含薑黃素多組成奈米複合物(Cur NP + VC和CC + VC)，並利用傅立葉轉換紅外線光譜、粉末X射線繞射光譜、奈米粒子粒徑分析儀和掃描式電子顯微鏡對薑黃素多組成奈米複合物進行結構及物性鑑定，進而進行其生物活性及體外傷口癒合之研究。
藉由體外試驗評估薑黃素藥物的釋放、複合物的抗氧化、抗菌和傷口癒合之研究。發現Cur NP + VC和CC + VC的兩種複合物的藥物釋放實驗顯示，薑黃素會從奈米複合物中慢慢持續地釋放出來。經過24小時後，約64.73%與66.85%的薑黃素分別從Cur NP + VC與CC + VC的複合藥物中釋放出來。利用DPPH試劑來評估含薑黃素奈米複合物的抗氧化活性，發現跟Cur NPs和Cur-Chi NPs奈米複合物相比，Cur NP + VC和CC + VC兩種奈米複合物的抗氧化活性有顯著地增加。以槲皮素作為抗氧化的對照組，發現Cur NP + VC和CC + VC的奈米複合物的抗氧化效力分別為80.56%和82.14%。抗氧化活性實驗數據證實，將薑黃素摻入奈米支架可增加其清除DPPH的能力。實驗利用薑黃素奈米複合物對大腸桿菌和金黃色葡萄球菌之抗菌作用進行了24小時的測試。數據結果顯示，跟單獨Cur NPs奈米藥物相比，Cur NP + VC奈米複合物對大腸桿菌和金黃色葡萄球菌的抗菌活性有顯著地提高。跟Cur-Chi NPs奈米複合物相比，CC + VC奈米複合物在抑制大腸桿菌和金黃色葡萄球菌的生長也有顯著的效果。實驗數據顯示，跟單一的幾丁聚醣、膠原蛋白、香草醛化合物或薑黃素奈米粒子相比，含薑黃素的奈米複合物具有明顯的抗菌活性。進行體外的細胞遷移試驗來分析薑黃素奈米複合物對於傷口的癒合研究，使NIH/3T3細胞單層上產生間隙，再分別用Cur NP + VC和CC + VC奈米複合物來處理，並在0、6、12和24小時監測其細胞遷移，實驗數據顯示，與未經處理的細胞相比，使用含薑黃素奈米複合物處理的細胞有眀顯的細胞遷移和間隙的閉合。發現經24小時後，使用Cur NP + VC奈米複合物和CC + VC奈米複合物處理的細胞傷口其傷口閉合率分別為85%和77%。
薑黃素的奈米複合物的研究顯示其抗氧化活性、對大腸桿菌和金黃色葡萄球菌的拮抗活性，及促進細胞遷移以增強細胞的傷口癒合皆與薑黃素的可持續釋放有關。薑黃素的奈米複合物的可生物降解及其持續性的局部給藥系統，可作為抗氧化劑、促進傷口癒合和預防細菌感染。薑黃素多組成奈米奈米複合物的有效生物活性特性亦可歸因於幾丁聚醣、膠原蛋白和香草醛的加乘效應。上述的實驗數據顯示本研究所製備的薑黃素奈米複合物出具有治療慢性傷口的創新治療策略。

Wound healing is one of the major challenges in chronic diseases, the current treatment options have less effective with undesirable side effects, and are expensive. Extensive research has being carried out to develop cost-effective, natural, biodegradable wound dressings that can reduce oxidative stress, inflammation and prevent bacterial infections. Curcumin has plethora of therapeutic applications; however, its low solubility limits its clinical use. In this study curcumin nanoparticles (Cur NPs) and curcumin-chitosan nanoparticles (Cur-Chi NPs) were incorporated into the vanillin-collagen (Van-Col) scaffold, which were further characterized and investigated their potential bioactivity, such as antioxidant and antibacteria, and wound healing properties. The nano scaffolds were prepared by freeze-drying method and were characterized using Fourier transform infrared spectroscopy, powder X-ray diffraction, nanoparticle tracking analysis and scanning electron microscopy.
The curcumin drug release, antioxidant, antibacterial and wound healing properties were assessed by in vitro assays. The drug release of Cur NP + VC and CC + VC showed a sustained released with time. Cur NP + VC reached about 64.73% of curcumin releasing, while it is 66.85% of curcumin being released from CC + VC after 24 hours. The antioxidant potential of the curcumin nanoparticle and its nano multiple component (nano scaffolds) were analyzed using DPPH reagent. The nanoparticle multiple of both Cur NP + VC and CC + VC showed significantly increased in antioxidant activity compared to that of Cur NPs and Cur-Chi NPs. Comparing to the antioxidant activity of quercetin being used as control, the antioxidant activity of both Cur NP + VC and CC + VC was 80.56% and 82.14%, respectively. These results suggest that incorporation of curcumin into nano scaffolds increases their DPPH scavenging activities. The curcumin nanoparticles were tested for their antibacterial effect against E. coli and S. aureus for 24 hours. The results clearly showed that the Cur NP + VC shows significantly higher antibacterial activity against E. coli and S. aureus than Cur NPs dies. Likewise, when compared to Cur-Chi NPs, the multiple component particle of CC + VC showed significantly effective in inhibiting the growth of E. coli and S. aureus. These results further demonstrate that encapsulating curcumin or Cur NPs into nano scaffolds has enhanced antibacterial activity compared to individual compounds. An in vitro scratch assay was performed to determine the wound healing properties of the curcumin nano scaffolds. For this assay, a gap was created on the NIH/3T3 cell monolayer and the cell migration in the cells treated with Cur NP + VC and CC + VC were monitored at 0, 6, 12 and 24 hours. According to the results the cells treated with curcumin nano scaffolds exhibited increased cell migration and gap closure after 24 hours compared to the untreated cells. The wound closure percentage of nano scaffold of Cur NP + VC and CC + VC treated cells showed about 85% and 77% wound closure after 24 hours, respectively.
The curcumin nano scaffolds showed sustained release of curcumin, which shows improving the antioxidant activity, antagonistic activity against E. coli and S. aureus and promote cell migration which enhanced wound healing in murine cell line. The curcumin nano scaffold is biodegradable and effective drug delivery system for topical use that can act as an antioxidant, facilitate wound healing, and prevent bacterial infections. The beneficial properties of the curcumin nano scaffolds can be attributed to the synergistic effect of chitosan, collagen and vanillin. Taken together these data suggest a promising scaffold that can accelerate wound healing and can be used as an innovative therapeutic strategy for treating chronic wounds.

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