Liposome intracellular delivery of Salvia miltiorrhiza Bge. deprivative DS-201 improves its BKCa channel-activating and vasorelaxing effects
Liposome intracellular delivery of Salvia miltiorrhiza Bge. deprivative DS-201 improves its BKCa channel-activating and vasorelaxing effects
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丹参的脂质体细胞内递送。
DOI：
10.1007/s11434-016-1046-6
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发表时间：
2016-04-01
期刊：
影响因子：
18.9
通讯作者：
Yang, Yan
中科院分区：
文献类型：
--
作者：
Yu, Lei;Cheng, Jun;Yang, Yan
一些药物在细胞内发挥治疗作用，但其亲水性阻碍了膜的穿透过程，从而限制了治疗效果，尽管这种性质保证了它们在水相中的溶解性。一个例子是丹参酮II-A磺酸钠(DS-201)，它是中草药丹参(丹参)的衍生物，它是BKCa通道开放剂和血管扩张剂。本研究建立并优化了一种能将DS-201包裹并输送到HEK293细胞中的脂质体给药系统。在单通道贴壁实验中，DS-201使BKCa通道的开放概率从基线的0.013+/-0.004增加到+40 mV时的0.036+/-0.011，并将电流密度从基线的23.2+/-4.4增加到+40 mV时的66.0+/-15.2 pF(P<；；0.05)，与细胞外直接给药相比。此外，DS-201脂质体对PE或PGF2a引起的血管收缩的抑制作用与对PE或PGF2a引起的血管收缩的抑制作用相似，但对大鼠肠系膜动脉的舒血管作用明显增强，与直接给药的20%抑制作用相似(P<；0.05)，提示脂质体提供的DS-201显著增强了药物的血管松弛作用。综上所述，本研究中优化的DS-201脂质体成功地将DS-201运送到细胞内，从而显著激活了BKCa通道，逆转了PE和PGF2α引起的收缩，证明了生物利用度的提高。
Some drugs exert curative effects intracellularly, but their hydrophilic property prohibits the membrane-penetrating process and thus limits the curative efficacies, although this property guarantee their solubility in aqueous phase. An example is sodium tanshinone II-A sulfonate (DS-201), a derivative of Chinese medical herb Danshen (Salvia miltiorrhiza) which is a BKCa channel opener and a vasodilator. This study established and optimized a liposome delivery system which could pack and deliver DS-201 into HEK293 cells transfected with BKCa channels, and DS-201 given this way significantly increased the open probability of BKCa channel from baseline 0.013 +/- 0.004 to 0.036 +/- 0.011 at +40 mV membrane potential (P < 0.05) in single-channel attached study, and also increased the current density from baseline 23.2 +/- 4.4 to 66.0 +/- 15.2 pA/pF at +40 mV membrane potential (P < 0.05), compared with the direct extracellular administration of this drug. Moreover, showing a similar to 60 % inhibition of the PE or PGF2a induced vascular constriction, the DS-201 liposomes did posses significantly enhanced vasorelaxant effect on rat mesenteric artery, compared with similar to 20 % inhibition of the directly administration of this drug (P < 0.05), suggesting that DS-201 delivered by liposomes significantly improved the drug's vasorelaxing effect. Taken together, the optimized DS-201 liposomes in our study successfully delivered DS-201 into cells and thus significantly activated BKCa channels to reverse the contraction induced by PE and PGF2 alpha, attesting the enhanced bioavailability.