当前位置：
X-MOL 学术
›
Eur. J. Pharm. Biopharm.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Passive permeability assay of doxorubicin through model cell membranes under cancerous and normal membrane potential conditions.
European Journal of Pharmaceutics and Biopharmaceutics ( IF 4.4 ) Pub Date : 2019-11-05 , DOI: 10.1016/j.ejpb.2019.10.011 Zahra Aminipour 1 , Mehran Khorshid 2 , Hamid Keshvari 3 , Shahin Bonakdar 4 , Patrick Wagner 2 , Bart Van der Bruggen 5
European Journal of Pharmaceutics and Biopharmaceutics ( IF 4.4 ) Pub Date : 2019-11-05 , DOI: 10.1016/j.ejpb.2019.10.011 Zahra Aminipour 1 , Mehran Khorshid 2 , Hamid Keshvari 3 , Shahin Bonakdar 4 , Patrick Wagner 2 , Bart Van der Bruggen 5
Affiliation
|
Doxorubicin is an anti-cancer drug that is important for breast cancer therapy. In this study, the effects of the membrane potential of breast cancer cells (-30 mV) and normal breast epithelial cells (-60 mV) on doxorubicin (DOX) permeability was studied. To achieve this goal, black lipid membranes (BLMs) as a model cell membrane were formed with DPhPC phospholipids in a single aperture of a Teflon sheet by the Montal and Mueller method. The presence of the BLM was characterized by capacitive measurements. The measured specific capacitance of 0.6 µF/cm2 after applying the Montal and Mueller method, confirming the presence of a BLM in the aperture. In addition, the very low current leakage of the BLM (9-24 pA) and ClyA-protein channel insertion in the BLM indicate the compactness, high quality, and thickness of 3-5 nm of the BLM. Afterwards, the permeability of doxorubicin through the BLM was studied at defined cell conditions (37 °C and pH 7.4), as well as cancerous and healthy epithelial-cell membrane potentials (-30 mV and -60 mV, respectively). The results show a slow DOX penetration within the first few hours, which increases rapidly with time. The initial slow penetration can be attributed to an electrostatic interaction between doxorubicin and DPhPC molecules in the model cell membrane. Furthermore, a MTT assay on MCF-10A and MCF-7 under different concentrations of doxorubicin confirmed that the cancerous MCF-7 cell line is more resistant to doxorubicin in comparison with the non-cancerous MCF-10A. Such studies highlight important strategies for designing and tuning the interaction efficacy of novel pharmaceuticals at molecular level.
中文翻译：
在癌性和正常膜电位条件下通过模型细胞膜进行阿霉素的被动渗透性测定。
阿霉素是一种抗癌药物，对乳腺癌的治疗很重要。在这项研究中，研究了乳腺癌细胞（-30 mV）和正常乳腺癌上皮细胞（-60 mV）的膜电位对阿霉素（DOX）渗透性的影响。为了实现该目标，通过Montal和Mueller方法在特氟龙片的单个孔中用DPhPC磷脂形成了作为模型细胞膜的黑色脂质膜（BLM）。BLM的存在通过电容测量来表征。在应用蒙塔尔（Montal）和穆勒（Mueller）方法之后，测得的比电容为0.6 µF / cm2，证实了孔径中存在BLM。另外，BLM的极低电流泄漏（9-24 pA）和Bly中ClyA蛋白通道的插入表明BLM的紧凑性，高质量和3-5 nm的厚度。然后，在限定的细胞条件下（37°C和pH 7.4）以及癌细胞和健康的上皮细胞膜电位（分别为-30 mV和-60 mV）研究了阿霉素通过BLM的渗透性。结果表明，在开始的几个小时内DOX渗透缓慢，并且随着时间的推移迅速增加。最初的缓慢渗透可归因于模型细胞膜中阿霉素与DPhPC分子之间的静电相互作用。此外，在不同浓度的阿霉素下对MCF-10A和MCF-7进行的MTT分析证实，与非癌性MCF-10A相比，癌性MCF-7细胞系对阿霉素的耐药性更高。此类研究突出了在分子水平上设计和调整新型药物相互作用功效的重要策略。
更新日期：2019-11-06
中文翻译：
在癌性和正常膜电位条件下通过模型细胞膜进行阿霉素的被动渗透性测定。
阿霉素是一种抗癌药物，对乳腺癌的治疗很重要。在这项研究中，研究了乳腺癌细胞（-30 mV）和正常乳腺癌上皮细胞（-60 mV）的膜电位对阿霉素（DOX）渗透性的影响。为了实现该目标，通过Montal和Mueller方法在特氟龙片的单个孔中用DPhPC磷脂形成了作为模型细胞膜的黑色脂质膜（BLM）。BLM的存在通过电容测量来表征。在应用蒙塔尔（Montal）和穆勒（Mueller）方法之后，测得的比电容为0.6 µF / cm2，证实了孔径中存在BLM。另外，BLM的极低电流泄漏（9-24 pA）和Bly中ClyA蛋白通道的插入表明BLM的紧凑性，高质量和3-5 nm的厚度。然后，在限定的细胞条件下（37°C和pH 7.4）以及癌细胞和健康的上皮细胞膜电位（分别为-30 mV和-60 mV）研究了阿霉素通过BLM的渗透性。结果表明，在开始的几个小时内DOX渗透缓慢，并且随着时间的推移迅速增加。最初的缓慢渗透可归因于模型细胞膜中阿霉素与DPhPC分子之间的静电相互作用。此外，在不同浓度的阿霉素下对MCF-10A和MCF-7进行的MTT分析证实，与非癌性MCF-10A相比，癌性MCF-7细胞系对阿霉素的耐药性更高。此类研究突出了在分子水平上设计和调整新型药物相互作用功效的重要策略。
京公网安备 11010802027423号