Yang Chang, Dai Xingxing, Yang Shufang, Ma Lina, Chen Liping, Gao Ruilin, Wu Xiaowen, Shi Xinyuan
Beijing University of Chinese Medicine, No. 11 of North 3rd Ring East Road, Chaoyang District, Beijing, 100029, China; Key Laboratory for Production Process Control and Quality Evaluation of Traditional Chinese Medicine, Beijing Municipal Science & Technology Commission, Beijing, 100029, China.
Beijing University of Chinese Medicine, No. 11 of North 3rd Ring East Road, Chaoyang District, Beijing, 100029, China; Key Laboratory of TCM-Information Engineer of State Administration of TCM, No. 11 of North 3rd Ring East Road, Chaoyang District, Beijing, 100029, China; Key Laboratory for Production Process Control and Quality Evaluation of Traditional Chinese Medicine, Beijing Municipal Science & Technology Commission, Beijing, 100029, China.
Colloids Surf B Biointerfaces. 2019 Nov 1;183:110462. doi: 10.1016/j.colsurfb.2019.110462. Epub 2019 Aug 27.
Transfersomes (TRS) can provide sustained drug delivery and themselves are biocompatible, biodegradable and nontoxic. Edge activators (EAs) are key factors for increasing the deformability of TRS, and this active deformation mechanism is of commercial interest, especially at the molecular level. Accordingly, in this paper, the deformability of pure dipalmitoyl phosphatidylcholine (DPPC) vesicles, TRS with sodium cholate as an EA, and DPPC vesicles containing pogostone (POG) were compared via umbrella sampling technology. The DPPC conformation and membrane fluidity of these three types of bilayer systems were evaluated, and the changes in the membrane properties of vesicles caused by EAs were studied. EAs could increase the deformability of TRS by decreasing the deformation energy barrier due to their amphiphilic structures, which was similar to those of DPPC molecules. The membrane properties also changed via treatment with EAs including altering the tail chain angle, disturbing the ordered tail chain arrangement and prompting lateral diffusion of DPPC molecules. In addition, the impact of EAs on DPPC bilayers was further demonstrated to be concentration dependent. An ideal concentration was identified for the lowest amount of EA that offered a gel-liquid-crystalline phase transition of DPPC bilayers. Importantly, POG, a lipophobic transdermal drug, can also affect the skin permeation behavior of vesicles but had weaker effects than EA.
传递体（TRS）能够实现药物的持续递送，并且自身具有生物相容性、可生物降解且无毒。边缘活化剂（EA）是提高传递体可变形性的关键因素，这种主动变形机制具有商业价值，尤其是在分子水平上。因此，本文通过伞形抽样技术比较了纯二棕榈酰磷脂酰胆碱（DPPC）囊泡、以胆酸钠作为边缘活化剂的传递体以及含有广藿香酮（POG）的DPPC囊泡的可变形性。评估了这三种双层体系的DPPC构象和膜流动性，并研究了边缘活化剂引起的囊泡膜性质变化。边缘活化剂因其两亲结构可降低变形能垒，从而提高传递体的可变形性，这与DPPC分子类似。通过边缘活化剂处理，膜性质也发生了变化，包括改变尾链角度、扰乱有序的尾链排列以及促进DPPC分子的横向扩散。此外，还进一步证明了边缘活化剂对DPPC双层膜的影响具有浓度依赖性。确定了一个理想浓度，该浓度下所需边缘活化剂的量最少，能使DPPC双层膜发生凝胶-液晶相转变。重要的是，疏脂性透皮药物广藿香酮也会影响囊泡的皮肤渗透行为，但其影响比边缘活化剂弱。
