新穎性白藜蘆醇奈米劑型的物理化學性質及抗氧化活性探討

The physicochemical and antioxidant activity research of novel resveratrol nanoparticles

黃浩偉(Hao-Wei Huang)

指導教授 ： 林俊清

高雄醫學大學/藥學院/天然藥物研究所碩士班/碩士(2010年)

摘要

白藜蘆醇具有良好之抗氧化、抗發炎、抗癌、抗真菌、神經保護、抗病毒活性，由於被發現可藉由其抗氧化之活性來預防心臟血管疾病而普受重視。惟其水溶解度不佳，生物可用率低，影響其生物利用之經濟效益。又前人之研究所製備之奈米劑型，對產率及溶解度之改善有限。因此本研究，設計了一種新的奈米劑型以改善這些缺點。本製劑是使用奈米沉降技術來奈米化白藜蘆醇。在本研究中，使用粒徑分析及穿透式電子顯微鏡去探討粒子大小與其分布情形，示差掃描熱分析儀及X光繞射儀來分析白藜蘆醇晶型結構的改變，並以傅立葉轉換紅外光儀和氫質子NMR來釐清分子間氫鍵結的關係。除了這些物理化學性質外，本研究為確定此奈米劑型在不同的pH下的溶離結果，並模擬不同體內環境中釋出情形，也以溶離試驗來分析白藜蘆醇及其奈米製劑在pH1.2(胃)、pH4.5(小腸)、pH7.4(血液)溶液之釋放情形。此外，進一步更以體外的抗氧化試驗，如DPPH自由基清除試驗、還原力測定、總抗氧化力、體外抗脂質過氧化活性試驗來證明本劑型之生物可用率的改善情況。由以上的物理化學性質及抗氧化試驗結果，證明新奈米化之白藜蘆醇劑型，粒子明顯的變小，晶型的消失，與賦形劑間之氫鍵的形成，抗氧化能力亦有提升，其還原力、DPPH自由基清除能力、脂質過氧化清除能力都有顯著的改善。期望這些結果可以增加白藜蘆醇奈米劑型在臨床藥物之可用性。

關鍵字

白藜蘆醇 ； 奈米製劑 ； 生物可用率 ； 溶解度 ； 抗氧化活性 ； pH值

並列摘要

Resveratrol (RES) has many pharmacological activities such as antioxidant, anticancer, and anti-inflammation. Previous studies have been showed that RES prevent heart disease by the antioxidant activity. Poor water solubility and bioavailability are the major disadvantages to limit clinical application. According that, the nanoprecipitation technique was used to prepare the novel resveratrol nanoparticle system (RESNP). In physicochemical characterization, particle size analysis (PCS) and transmission electron microscopy (TEM) were used to realize the changes of the particles size distribution and morphology. The differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD) were used to analyze the changes of crystal structure of RES. Fourier transform infrared spectroscopy (FT-IR) and 1H nuclear magnetic resonance (1H NMR) were used to figure out the intermolecular hydrogen bonding of polymer and RES. Moreover, the dissolution releases of RES and RESNP were determined in different pH solution. In addition, several antioxidant assays were used to compare the antioxidant activities of RES and RESNP with DPPH radical scavenging, reducing power, Trolox equivalent antioxidant capacity, and anti-lipid peroxidation. As results showed, RESNP could increase the dissolution property by particles size reduction, amorphous and hydrogen bounding. On the other hand, RESNP was presented more potent antioxidant activities than RES. Finally, the RESNP could be further developed for clinical trials.

並列關鍵字

Resveratrol ； Nanoparticles ； Physicochemical characterization ； Antioxidant activity

參考文獻

1. Droge, W. (2002). "Free Radicals in the Physiological Control of Cell Function." Physiol. Rev. 82(1): 47-95.

2. Blokhina, O., Virolainen, E, et al. (2003). "Antioxidants, Oxidative Damage and Oxygen Deprivation Stress: a Review." Ann Bot 91(2): 179-194.

3. Yen, F.-L., T.-H. Wu, et al. (2007). "Hepatoprotective and antioxidant effects of Cuscuta chinensis against acetaminophen-induced hepatotoxicity in rats." Journal of Ethnopharmacology 111(1): 123-128.

4. Kanadaswami, C., Lee, L.T., Lee, P.P., Hwang, J.J., Ke, F.C., Huang, Y.T., Lee, M.T., (2005). The antitumor activeites of flavonoids. In Vivo. 19,895-909.

5. Fang, Y.-Z., S. Yang, et al. (2002). "Free radicals, antioxidants, and nutrition." Nutrition 18(10): 872-879.