School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China.
Key Laboratory for Production Process Control and Quality Evaluation of Traditional Chinese Medicine, Beijing Municipal Science & Technology Commission, Beijing, 100029, China.
AAPS PharmSciTech. 2020 May 17;21(5):138. doi: 10.1208/s12249-020-01680-6.
Physical stability is one of critical characteristics of liposome, especially to its clinical application. Vesicle fusion was one of the common physical stability phenomena that occurred during the long storage period. Because vesicle fusion could be easily checked by the change of vesicle size, it was widely applied in the evaluation of liposome physical stability. However, since the method requires the liposome to be placed under certain conditions for long-term observation, a liposome physical stability test usually takes several weeks, which greatly hinders the research efficiency. In this study, to speed up the research efficiency, coarse-grained molecular dynamics was first applied in the study of liposome physical stability. By analyzing the microprocess of vesicle fusion, two parameters including diffusion constant and the total time of the vesicle morphology transition process were employed to study the liposome physical stability. Then, in order to verify the applicability of two parameters, the physical stability of elastic liposomes and conventional liposomes was compared at 3 different temperatures. It was found that the fusion probability and speed of elastic liposomes were higher than those of conventional liposomes. Thus, elastic liposomes showed a worse physical stability compared with that of conventional liposomes, which was consistent with former research. Through this research, a new efficient method based on coarse-grained molecular dynamics was proposed for the study of liposome physical stability.
物理稳定性是脂质体的关键特性之一，尤其是对其临床应用而言。囊泡融合是脂质体在长期储存过程中发生的常见物理稳定性现象之一。由于囊泡融合可以通过囊泡大小的变化来轻松检测，因此它被广泛应用于脂质体物理稳定性的评估。然而，由于该方法需要将脂质体置于某些条件下进行长期观察，因此脂质体物理稳定性测试通常需要数周时间，这极大地阻碍了研究效率。在这项研究中，为了提高研究效率，首先在脂质体物理稳定性研究中应用了粗粒化分子动力学。通过分析囊泡融合的微观过程，使用扩散常数和囊泡形态转变过程的总时间这两个参数来研究脂质体的物理稳定性。然后，为了验证这两个参数的适用性，在 3 种不同温度下比较了弹性脂质体和常规脂质体的物理稳定性。结果发现，弹性脂质体的融合概率和速度均高于常规脂质体。因此，与之前的研究一致，弹性脂质体的物理稳定性比常规脂质体差。通过这项研究，提出了一种基于粗粒化分子动力学的新的脂质体物理稳定性研究的高效方法。
