顺铂热敏脂质体对C26荷瘤BALB / c小鼠轻度热疗的治疗作用,Molecular Pharmaceutics

当前位置： X-MOL 学术 › Mol. Pharmaceutics › 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.)

顺铂热敏脂质体对C26荷瘤BALB / c小鼠轻度热疗的治疗作用
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2017-02-14 00:00:00 , DOI: 10.1021/acs.molpharmaceut.6b01006
Seyedeh Hoda Alavizadeh ₁ , Fatemeh Gheybi ₂ , Amin Reza Nikpoor ₃ , Ali Badiee ₄ , Shiva Golmohammadzadeh ₄ , Mahmoud Reza Jaafari ₁

Affiliation

这项研究报告了在DPPC / MSPC / PEG ₂₀₀₀ -DSPE基质（90/10/4）和轻度高温（HT）（42°C）中掺入不同HSPC比率的热敏脂质体（TSL）的活性。通过被动平衡方法，在TSL中加载了膜渗透性差的抗癌药物顺铂。将HSPC添加到相应的DPPC脂质基质中会提高转变温度。体外数据表明，在42°C下10分钟内，纳米级DPPC 90溶-TSL（LTSL）的顺铂渗漏率> 90％，而其他带有HSPC的TSL表现出更大的稳定性。与其他制剂相比，顺铂的血浆动力学表明在头4小时内从DPPC 90-LTSL泄漏的顺铂更高（从17.4至0.4μg/ mL）。实际上，增加脂质体双层中的HSPC分数可以显着改善药物在血液中的保留率。尽管DPPC 90-LTSL加一步HT有望提供独特的药物释放，但过早的药物泄漏以及大部分药物可能冲回血液循环导致存活率降低。另一方面，稳定的DPPC 30 / HSPC 60 / MSPC 10 / PEG ₂₀₀₀-DSPE 4脂质体加两步HT大大提高了动物的存活率。特别地，与其他制剂相比，在两步轻度HT中通过稳定的DPPC 30 / HSPC 60 / MSPC 10 / PEG ₂₀₀₀ -DSPE 4脂质体改善的顺铂递送增强了抗肿瘤功效。因此，癌细胞通过稳定的脂质体长时间暴露于顺铂将是提高动物存活率的有效方法。

"点击查看英文标题和摘要"

Therapeutic Efficacy of Cisplatin Thermosensitive Liposomes upon Mild Hyperthermia in C26 Tumor Bearing BALB/c Mice

This study reports on the activity of thermosensitive liposomes (TSLs) incorporating different HSPC ratios in DPPC/MSPC/PEG₂₀₀₀-DSPE matrix (90/10/4) plus mild hyperthermia (HT) (42 °C). TSLs were loaded with a poorly membrane permeable anticancer drug, cisplatin, through the passive equilibration method. The addition of HSPC to the corresponding DPPC lipid matrix increased the transition temperature. In vitro data demonstrated >90% cisplatin leakage from nanosized DPPC 90-lyso-TSL (LTSL) within 10 min at 42 °C, while other TSLs bearing HSPC showed greater stability. The plasma kinetics of cisplatin demonstrated higher cisplatin leakage from DPPC 90-LTSL in the first 4 h (from 17.4 to 0.4 μg/mL) compared to other formulations. Indeed, increasing HSPC fraction in liposome bilayers significantly improved drug retention in blood. Though DPPC 90-LTSL plus one-step HT was expected to provide a unique drug release, the premature drug leakage as well as the likely wash-back of a great portion of drug into the blood circulation resulted in reduced survival. On the other hand, stabilized DPPC 30/HSPC 60/MSPC 10/PEG₂₀₀₀-DSPE 4 liposomes plus two-step HT greatly enhanced the survival of animals. In particular, the improved delivery of cisplatin through stabilized DPPC 30/HSPC 60/MSPC 10/PEG₂₀₀₀-DSPE 4 liposomes in two-step mild HT enhanced antitumor efficacy compared to other formulations. Thus, prolonged exposure of cancer cells to cisplatin through stabilized liposomes would be an efficient approach in improving the survival of animals.

更新日期：2017-02-14

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南