Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Melbourne, Victoria 3052, Australia.
Drug Deliv Transl Res. 2012 Aug;2(4):284-92. doi: 10.1007/s13346-012-0064-4. Epub 2012 Mar 3.
The characterization of encapsulation efficiency and in vitro drug release from nanoparticle-based formulations often requires the separation of nanoparticles from unencapsulated drug. Inefficient separation of nanoparticles from the medium in which they are dispersed can lead to inaccurate estimates of encapsulation efficiency and drug release. This study establishes dynamic light scattering as a simple method for substantiation of the effectiveness of the separation process. Colistin-loaded liposomes, as an exemplar nano-sized delivery particle, were diluted to construct a calibration curve relating the amount of light scattering to liposome concentration. Dynamic light scattering revealed that, in the case of ultracentrifugation and centrifugal ultrafiltration, approximately 2.9% of the total liposomes remained in supernatants or filtrates, respectively. In comparison, filtrates obtained using pressure ultrafiltration contained less than 0.002% of the total liposomes from the formulation. Subsequent release studies using dialysis misleadingly implied a slow release of colistin over >48 h. In contrast, pressure ultrafiltration revealed immediate equilibration to the equilibrium distribution of colistin between the liposome and aqueous phases upon dilution. Pressure ultrafiltration is therefore recommended as the optimal method of choice for studying release kinetics of drug from nanomedicine carriers.
纳米粒子制剂的包封效率和体外药物释放的特性通常需要将纳米粒子与未包裹的药物分离。如果不能有效地将纳米粒子从分散它们的介质中分离出来，就会导致对包封效率和药物释放的不准确估计。本研究确立了动态光散射作为验证分离过程有效性的简单方法。多粘菌素负载脂质体作为一个示例纳米级递药粒子，被稀释以构建一个与脂质体浓度相关的光散射量的校准曲线。动态光散射表明，在超速离心和离心超滤的情况下，分别有约 2.9%的总脂质体残留在上清液或滤出液中。相比之下，使用压力超滤获得的滤出液中，制剂中总脂质体的含量小于 0.002%。随后使用透析进行的释放研究错误地暗示了多粘菌素在超过 48 小时内的缓慢释放。相比之下，压力超滤在稀释后立即达到多粘菌素在脂质体和水相之间的平衡分布。因此，建议压力超滤作为研究纳米药物载体中药物释放动力学的最佳方法。
