卡巴拉汀脂质体的制备及其大鼠鼻腔给药的药物动力学
Preparation of rivastigmine liposome and its pharmacokinetics in rats after intranasal administration
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摘要:
制备卡巴拉汀脂质体, 研究其在大鼠鼻腔给药的药代动力学。采用硫酸铵梯度法制备包载卡巴拉汀 的脂质体, 考察粒径、zeta电位和包封率, 测定脂质体在磷酸盐缓冲液中的释放; 大鼠鼻腔给予卡巴拉汀脂质体, 以安替比林为内标, 采用高效液相色谱−串联质谱法 (HPLC/MS) 测定血浆中卡巴拉汀的浓度, 运用DAS 2.0 软件拟合药代动力学参数。经筛选制备的脂质体包封率为 (33.41 ± 6.58) %, 平均粒径在154~236 nm, zeta电位 (−10.47 ± 2.41) mV。脂质体的体外释放符合一级动力学方程。大鼠鼻腔给药后, Cmax, Tmax和AUC0−∞分别为 (1.50 ± 0.15) mg·L−1, 15 min和 (89.06 ± 8.30) mg·L−1·min。卡巴拉汀制备成脂质体经大鼠鼻腔给药后, 吸收迅速, 血药浓度可以达到一定水平。
Abstract:To prepare rivastigmine liposome, rivastigmine was loaded into liposome via ammonium sulfate gradient method. Its pharmacokinetic profile in rats was evaluated after intranasal administration. The size, zeta potential, entrapped efficiency and release of rivastigmine from the liposome in vitro were determined. Plasma concentration of rivastigmine was determined by high performance liquid chromatography-tandem mass spectrometry (HPLC/MS) using antipyrine as internal standard. The pharmacokinetic parameters were calculated by DAS 2.0. The entrapped efficiency of rivastigmine liposome was (33.41 ± 6.58) %, with the mean diameter of 154−236 nm and zeta potential of (−10.47 ± 2.41) mV. The release behavior of rivastigmine was fitting the first order equation in vitro. The pharmacokinetic studies indicated that the Cmax, Tmax and AUC0−∞ of rivastigmine liposome were (1.50 ± 0.15) mg·L−1, 15 min and (89.06 ± 8.30) mg·L−1·min, respectively. Rivastimine liposome was absorbed rapidly, and could reach a certain concentration in rat plasma after intranasal delivery.
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