阿仑膦酸钠脂质体的制备及透皮给药性能评价

目的 筛选制备阿仑膦酸钠（ALN）脂质体的最佳条件并探究其体外透皮性能。方法 通过薄膜水合法结合过膜挤压法制备ALN脂质体，计算包封率和载药量，并采用双室立式透皮扩散池考察药物的渗透性，计算累积渗透量和释放模型的拟合。结果 通过单因素实验得到制备脂质体的最佳条件为膜材比2.5∶1、转速700 r•min^-1、脂药比10∶1、超声时间6 min、水化温度45 ℃、包封率和载药效率最大分别为49.6%和14%。ALN脂质体的累积渗透量最大为814.78 μg•cm^-2 相当于原液的两倍。且原液的释放模型基本符合Ritger-peppas方程，ALN脂质体的释放模型基本符合零级动力学方程，具有一定的缓控释作用。结论 所制备的ALN脂质体均匀稳定，含ALN的脂质体具有良好的透皮效果，因此证明了将ALN制成脂质体的可行性，同时也为外用新剂型的研究提供了思路，具有良好的发展前景。

Preparation and evaluation of transdermal delivery properties of alendronate sodium liposomes

Objective To screen the optimal conditions for the preparation of alendronate sodium (ALN) liposomes and to investigate their in vitro transdermal properties.Methods ALN liposomes were prepared by film hydration combined with periplasmic extrusion, the encapsulation rate and drug loading capacity were calculated, and the permeability of the drug was investigated by using a two-compartment vertical transdermal diffusion cell to calculate the cumulative permeation and the fitting of the release model.Results The optimal conditions for the preparation of liposomes were 2.5∶1 membrane ratio, 700 r•min^-1 rotational speed, 10∶1 lipid-drug ratio, 6 min ultrasonication time, 45 ℃ hydration temperature, 49.6% encapsulation rate and 14% loading efficiency, respectively, and the cumulative permeation amount of ALN liposomes was 814.78 μg•cm^-2, which was twice as much as that of the stock solution. The release model of the stock solution was basically in accordance with the Ritger-peppas equation, and the release model of ALN liposomes was basically in accordance with the zero-order kinetic equation, which has a certain effect of slow and controlled release.Conclusion The prepared ALN liposomes were homogeneous and stable, and the ALN-containing liposomes had a good transdermal effect, thus proving the feasibility of making ALN into liposomes, and also providing ideas for the research of new dosage forms for topical application, which has a good prospect for development.