越来越多研究发现，线粒体功能障碍会引起多种疾病，其中包括癌症、神经退行性疾病、肥胖、糖尿病和遗传性线粒体疾病，针对这些疾病，有效的治疗是把治疗药物靶向到线粒体中。随着研究的深入，多种线粒体靶向载药系统被开发出来，相比于其他线粒体靶向载药系统，线粒体靶向脂质体不但具有靶向性，还可以改善药物的理化性质，降低药物毒性。因此，高效、低毒的线粒体靶向脂质体成为近年研究的热点。

研究表明，白藜芦醇是一种很有前景的抗氧化类药物，对心血管具有双向调节作用，能改善微循环，具有显著的抗炎、抗突变、抗氧化、抗自由基以及抑制血小板聚集的作用，具有预防动脉硬化、防止冠心病、降低血清和肝脏的脂质、保护肝脏以及抗癌等多方面的活性。为了制备线粒体靶向白藜芦醇脂质体，我们首先合成线粒体靶向分子TPGS₁₀₀₀-TPP，并使用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)和HNMR对其进行结构鉴定，然后使用薄膜分散法制备线粒体靶向脂质体，通过单因素实验和正交实验，以包封率、粒径、分散性指数（PDI）作为评价指标，考察脂质体的制备工艺和条件，获得最优制备工艺。当药脂比=1:25，胆固醇和磷脂的质量比=1:20，水化温度为60℃，水化时间为2h，探头超声时间为10min，制备的脂质体粒径均匀、包封率高。

我们建立了白藜芦醇的HPLC含量测定方法，并在日内精密度(Intra-day precision)和日间精密度（Inter-day precision）、稳定性实验（Stability test）、重复性实验（Repeatability test）等方法学上进行了验证，表明该方法简单、灵敏度高、准确度高、稳定性好，可以用于白藜芦醇的含量检测，为下一步脂质体的质量评价提供基础。然后从包封率、粒径分布、分散性指数（PDI）、Zeta电势、透射电镜观察脂质体的形态、初步稳定性、释放度等几个方面考察制备的脂质体质量，结果显示，制备的脂质体外形圆整，大小均一，稳定性好，具有一定的缓释效果。

实验中我们采用中性红实验检测不同浓度载药脂质体对皮肤成纤维细胞（CCC-ESF）的细胞毒性，结果表明，在0-50μg/ml浓度范围内，药物浓度与毒性呈正相关。相同白藜芦醇浓度时，线粒体靶向白藜芦醇脂质体比白藜芦醇脂质体和线粒体靶向空白脂质体的细胞毒性更大。

It has been progressively evident that mitochondrial dysfunction is responsible for a variety of human diseases, including cancer, neurodegenerative diseases, obesity, diabetes and inherited mitochondrial diseases. Effective medical therapies for such diseases  require the targeted delivery of therapeutic agents to mitochondria. With further research, many mitochondria targeting drug delivery systems have been developed, Comparing to other mitochondria targeting drug delivery system, mitochondria targeting liposomes not only has targeting ability, but also can improve the pharmaceutical properties of drugs, and accordingly, decreases their systemic toxicity. Hence, development of low toxic effective mitochondrial targeting liposomes has been the focus of mitochondria targeting drug delivery field in recent years.

Research shows that resveratrol is a promising antioxidant agent, Resveratrol has a dual regulating function in cardiovascular diseases, which could improve microcirculation of blood vessels. It also has a protective effects including anti-inflammatory, anti-mutation, antioxidant, scavenging free radical and inhibition of platelet aggregation. Arteriosclerosis and coronary heart diseases were found to be prevented by resveratrol. Its pharmacodynamic activities include many aspects such as reducing the lipid of blood and liver, protecting the liver, and cancer-combating. To prepare the mitochondria targeted resveratrol liposomes, we firstly synthesized mitochondrial targeting molecule TPGS₁₀₀₀-TPP, and its structure was confirmed using MALDI-TOF-MS and HNMR. Targeting resveratrol liposomes were prepared using the film dispersion method. A single factor and orthogonal design optimization were utilized to optimize the preparation process. The encapsulation efficiency, particle size, and polydispersity index (PDI) were adopted to evaluate the characterization of the liposomes. The optimized preparation method includes: 1)the mass ratio of resveratrol and phospholipid is 1:25,2)the mass ratio of cholesterol and phospholipid is 1:20. The lipid film was hydrated with phosphate buffered saline for 2h at 60℃, followed by sonication using an ultrasonic cell disruptor for 10 min. The liposomes had high encapsulation efficiency and uniform particle size when this method was adopted.

We have established a method for determination of the content of resveratrol by HPLC and evaluated by intra-day precision test, inter-day precision test, stability test and repeatability test. Methodology validation showed that the method was simple, highly sensitive, highly accurace, stabile, and can be used to detect resveratrol. The characterization of mitochondria targeting resveratrol liposomes were evaluated by encapsulation efficiency, particle size distribution, PDI, and Zeta potential. Transmission Electron Microscopy was used to assess the morphology. The results showed that liposomes had rounded shape, uniform particle size, good stability and a sustained release effects.

Neutral red assay was used to determine the cell toxicity of loaded drug liposome on CCC-ESF cells. The results showed that there was a positive correlation between drug concentration and cell toxicity in the range of 0-50μg/ml. At the same resveratrol concentration, the cytotoxicity of mitochondria targeted resveratrol liposomes were greater than resveratrol liposome and blank mitochondrial targeting liposomes.