Fabrication of bone scaffolds with sequential delivery of SDF-1 and MGF and study on their synergistic effect on bone regeneration

Abstract

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.