Molecular Dynamics Studies of Liposomes as Carriers for Photosensitizing Drugs: Development, Validation, and Simulations with a Coarse-Grained Model
Molecular Dynamics Studies of Liposomes as Carriers for Photosensitizing Drugs: Development, Validation, and Simulations with a Coarse-Grained Model
复制标题
DOI：
10.1021/ct400466m
复制
发表时间：
2014-01-01
影响因子：
5.5
通讯作者：
Eriksson, Leif A.
中科院分区：
文献类型：
--
作者：
Jambeck, Joakim P. M.;Eriksson, Emma S. E.;Eriksson, Leif A.
脂质体被提出作为药物递送系统，并且原则上可以被设计成与特定组织类型或局部环境结合。然而，关于药物递送的确切机制和药物分子在脂质载体内的分布的细节知之甚少。在目前的工作中，开发了一种粗粒（CG）脂质体模型，由超过2500个脂质组成，具有不同程度的药物负载。对于药物分子，我们选择金丝桃素，一种天然化合物，提出用于光动力疗法，其中CG模型推导和基准对相应的原子膜双层模型模拟。产生具有21-84个金丝桃素分子的脂质体，并进行10微秒的模拟。本文报道了金丝桃素的分布、它们在脂质双层内的取向以及用于将金丝桃素分子从内部水性“液滴”通过脂质体双层转移的平均力的潜力。
Liposomes are proposed as drug delivery systems and can in principle be designed so as to cohere with specific tissue types or local environments. However, little detail is known about the exact mechanisms for drug delivery and the distributions of drug molecules inside the lipid carrier. In the current work, a coarse-grained (CG) liposome model is developed, consisting of over 2500 lipids, with varying degrees of drug loading. For the drug molecule, we chose hypericin, a natural compound proposed for use in photodynamic therapy, for which a CG model was derived and benchmarked against corresponding atomistic membrane bilayer model simulations. Liposomes with 21-84 hypericin molecules were generated and subjected to 10 microsecond simulations. Distribution of the hypericins, their orientations within the lipid bilayer, and the potential of mean force for transferring a hypericin molecule from the interior aqueous "droplet" through the liposome bilayer are reported herein.