Liposome intracellular delivery of Salvia miltiorrhiza Bge. deprivative DS-201 improves its BKCa channel-activating and vasorelaxing effects
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- 作者：Lei Yu ; Jun Cheng ; Wen-Jun Huang ; Xiao-Qiu Tan ; Liang Mao ; Zhi-Fei Liu…
- 刊名：Chinese Science Bulletin
- 出版年：2016
- 出版时间：April 2016
- 年：2016
- 卷：61
- 期：8
- 页码：622-631
- 全文大小：1,435 KB
- 刊物主题：Science, general; Life Sciences, general; Physics, general; Chemistry/Food Science, general; Earth Sciences, general; Engineering, general;
- 出版者：Springer Berlin Heidelberg
- ISSN：1861-9541
- 卷排序：61
文摘
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 ~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 ~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 PGF2α, attesting the enhanced bioavailability.KeywordsDrug delivery systemLiposomeSodium tanshinone II-A sulfonateBKCa channelVasodilatation