Jeong Dooyong, Lee Don Haeng, Lee Dong Ki, Na Kun
Department of Biotechnology, The Catholic University of Korea, Bucheon-si, Gyeonggi-do, Korea.
Utah-Inha DDS and Advanced Therapeutics Research Center, College of Medicine, Inha University, Nam-Ku, Incheon, Korea.
J Biomater Appl. 2015 Mar;29(8):1133-44. doi: 10.1177/0885328214552712. Epub 2014 Sep 24.
To increase the therapeutic potency of nonvascular drug-eluting stents, sodium caprate was employed as a drug-penetration enhancer. A polytetrafluoroethylene-covered drug-eluting stent was coated with a mixture containing sodium caprate, paclitaxel, and polyurethane via the rolling coating technique. The coated stent has a smooth membrane surface with a 40-µm membrane thickness. Paclitaxel was released from the coated stent for two months. In the multilayered cell sheet model, sodium caprate in the polyurethane membrane (PUSC10) showed the possibility of enhancing the paclitaxel tissue penetration. The amount of penetrated paclitaxel for the sodium caprate-containing polyurethane membrane (PUSC10) was two times higher than that of sodium caprate-free polyurethane membrane. Additionally, the potential of sodium caprate was confirmed by a tumor-bearing small animal model. PUSC10 incorporated with Nile red (as a model fluorescence dye for visualization of drug penetration; PUSC10-Nile red) or PUSC10 incorporated with paclitaxel (PUSC10-paclitaxel) membrane was implanted at tumor sites in Balb/c mice. In the case of PUSC10-Nile red, the tissue penetration depth of Nile red was significantly increased from 30 µm (without sodium caprate) to 1060 µm (with sodium caprate). After seven days, an almost four times higher therapeutic area of PUSC10-paclitaxel was observed compared to that of polyurethane-paclitaxel (without sodium caprate) by a terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The results indicate that sodium caprate improves the penetration and therapeutic efficiencies of drugs in drug-eluting stents, and thus, it has potential for local stent therapy.
为提高非血管药物洗脱支架的治疗效果，采用癸酸钠作为药物渗透增强剂。通过滚涂技术，在聚四氟乙烯涂层的药物洗脱支架上涂覆含有癸酸钠、紫杉醇和聚氨酯的混合物。涂覆后的支架具有光滑的膜表面，膜厚度为40μm。紫杉醇从涂覆后的支架中释放两个月。在多层细胞片模型中，聚氨酯膜（PUSC10）中的癸酸钠显示出增强紫杉醇组织渗透的可能性。含癸酸钠的聚氨酯膜（PUSC10）的紫杉醇渗透量比不含癸酸钠的聚氨酯膜高两倍。此外，通过荷瘤小动物模型证实了癸酸钠的潜力。将掺入尼罗红（作为用于可视化药物渗透的模型荧光染料；PUSC10-尼罗红）的PUSC10或掺入紫杉醇的PUSC10（PUSC10-紫杉醇）膜植入Balb/c小鼠的肿瘤部位。在PUSC10-尼罗红的情况下，尼罗红的组织渗透深度从30μm（无癸酸钠）显著增加到1060μm（有癸酸钠）。七天后，通过末端脱氧核苷酸转移酶dUTP缺口末端标记分析观察到，与聚氨酯-紫杉醇（无癸酸钠）相比，PUSC10-紫杉醇的治疗面积几乎高出四倍。结果表明，癸酸钠可提高药物洗脱支架中药物的渗透和治疗效率，因此，它在局部支架治疗方面具有潜力。
