摘要
Some drugs exert curative effects intracellu- larly, but their hydrophilic property prohibits the mem- brane-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 BKc~ channel opener and a vasodilator. This study established and opti- mized 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 -4- 0.011 at -t-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 4- 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 constric- tion, 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 PGF2a, attesting the enhanced bioavailability.
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 BK_(Ca) 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 BK_(Ca) channels, and DS-201 given this way significantly increased the open probability of BK_(Ca) channel from baseline 0.013 ± 0.004 to 0.036 ± 0.011 at +40 m V membrane potential(P \ 0.05) in single-channel attached study, and also increased the current density from baseline23.2 ± 4.4 to 66.0 ± 15.2 p A/p F at +40 m V membrane potential(P \ 0.05), compared with the direct extracellular administration of this drug. Moreover, showing a *60 %inhibition of the PE or PGF2 a 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 BK_(Ca) channels to reverse the contraction induced by PE and PGF2 a, attesting the enhanced bioavailability.
基金
supported by the National Natural Science Foundation of China(30670763
81173661
31300948)
the Sichuan Technology and Education Committee(2011FZ0106and XYTD201005
09ZZ010)
