Degim Z, Mutlu N B, Yilmaz S, Eşsiz D, Nacar A
Department of Pharmaceutical Technology, Gazi University Faculty of Pharmacy, Ankara, Turkey.
Pharmazie. 2010 Jan;65(1):32-40.
Transportations of rivastigmine containing liposomes across Caco-2 cells were studied and in vitro test results were compared with in vivo results. MTT test was used for cell viability studies. Series of formulations were prepared containing rivastigmine which is used for the treatment of Alzheimer's disease. Characterization and stability studies for liposome formulations were performed. Encapsulation efficiencies of liposomes were 35.4%, 25.2% and 29.9% for rivastigmine, rivastigmine-sodium taurocholate, rivastigmine-dimethyl-beta-CD liposomes, respectively. In stability studies, particle size and size distribution, zeta potential, rivastigmine amounts were determined and shelf lives of liposomes were calculated. Penetration properties of rivastigmine through Caco-2 cells, dialysis membrane and kinetics of release from liposomes were determined. Permeability coefficients were calculated after diffusion studies. The highest value of % cumulative amount of rivastigmine passed through caco-2 cell cultures was found to be 87.2% for rivastigmine-sodium taurocholate solution and 12.8% for rivastigmine-sodium taurocholate liposome. The highest permeability coefficient value was obtained with sodium taurocholate liposomes for -0.75. Rivastigmine liposomes and solutions were also applied to animals. Acetyl choline esterase (AChE) activity was determined by the Ellman method on mice. %AChE inhibition values were calculated using blood and brain tissue samples. The physical appearances of the brains were investigated by TEM microscope. The highest value of AChE inhibition was observed for rivastigmine and sodium taurocholate liposomes. The histological investigations and observations also supported these results.
研究了含卡巴拉汀的脂质体跨Caco-2细胞的转运情况，并将体外测试结果与体内结果进行了比较。采用MTT试验进行细胞活力研究。制备了一系列含用于治疗阿尔茨海默病的卡巴拉汀的制剂。对脂质体制剂进行了表征和稳定性研究。卡巴拉汀、卡巴拉汀-牛磺胆酸钠、卡巴拉汀-二甲基-β-环糊精脂质体的脂质体包封率分别为35.4%、25.2%和29.9%。在稳定性研究中，测定了粒径和粒径分布、zeta电位、卡巴拉汀含量，并计算了脂质体的保质期。测定了卡巴拉汀透过Caco-2细胞、透析膜的渗透特性以及从脂质体中的释放动力学。扩散研究后计算了渗透系数。发现卡巴拉汀-牛磺胆酸钠溶液通过caco-2细胞培养物的卡巴拉汀累积量百分比最高值为87.2%，卡巴拉汀-牛磺胆酸钠脂质体为12.8%。牛磺胆酸钠脂质体的最高渗透系数值为-0.75。卡巴拉汀脂质体和溶液也应用于动物。采用Ellman法测定小鼠的乙酰胆碱酯酶（AChE）活性。使用血液和脑组织样本计算%AChE抑制值。通过透射电子显微镜研究了大脑的外观。观察到卡巴拉汀和牛磺胆酸钠脂质体的AChE抑制值最高。组织学研究和观察也支持了这些结果。
