Touitou Elka, Natsheh Hiba, Duchi Shaher
The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem 91120, Israel.
Pharmaceutics. 2018 Jul 3;10(3):82. doi: 10.3390/pharmaceutics10030082.
The aim of this work was to design and characterize a new nanovesicular nasal delivery system (NDS) containing buspirone, and investigate its efficiency in an animal model for the treatment of hot flushes. The presence of multilamellar vesicles with a mean size distribution of 370 nm was evidenced by transition electron microscopy (TEM), cryo-scanning electron microscopy (Cryo-SEM), and dynamic light scattering (DLS) tests. Pharmacodynamic evaluation of the nasal treatment efficacy with the new system was carried out in ovariectomized (OVX) rat—an animal model for hot flushes—and compared with other treatments. We found that the nasal administration of a buspirone NDS resulted in a significant reduction in tail skin temperature (TST). This effect was not observed in the control buspirone-treated groups. Buspirone levels in the plasma and brain of nasally-treated normal rats were quantified and compared with those of rats that had received oral administration by a LC-MS/MS assay. A significantly higher bioavailability was achieved with the new treatment relative to an oral administration of the same drug dose. No pathological changes in the nasal cavity were observed following sub-chronic nasal administration of buspirone NDS. In conclusion, the data of our investigation show that buspirone in the new nanovesicular nasal carrier could be considered for further studies for the development of a treatment for the hot flushes ailment.
这项工作的目的是设计并表征一种含有丁螺环酮的新型纳米囊泡鼻腔给药系统（NDS），并在动物模型中研究其治疗潮热的效果。通过透射电子显微镜（TEM）、冷冻扫描电子显微镜（Cryo-SEM）和动态光散射（DLS）测试证实了存在平均尺寸分布为370 nm的多层囊泡。在去卵巢（OVX）大鼠（一种潮热动物模型）中对新系统的鼻腔治疗效果进行了药效学评估，并与其他治疗方法进行了比较。我们发现，丁螺环酮NDS鼻腔给药可使尾皮肤温度（TST）显著降低。在对照丁螺环酮治疗组中未观察到这种效果。通过液相色谱-串联质谱（LC-MS/MS）测定法对经鼻腔治疗的正常大鼠血浆和脑中的丁螺环酮水平进行了定量，并与口服给药的大鼠进行了比较。与口服相同药物剂量相比，新治疗方法的生物利用度显著更高。在丁螺环酮NDS亚慢性鼻腔给药后，未观察到鼻腔的病理变化。总之，我们的研究数据表明，新纳米囊泡鼻腔载体中的丁螺环酮可考虑用于进一步研究以开发潮热疾病的治疗方法。
