Tomoda Keishiro, Watanabe Aya, Suzuki Kenichi, Inagi Toshio, Terada Hiroshi, Makino Kimiko
Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
Colloids Surf B Biointerfaces. 2012 Sep 1;97:84-9. doi: 10.1016/j.colsurfb.2012.04.002. Epub 2012 Apr 13.
Estradiol is a therapeutic agent for treatment of perimenopausal symptoms and osteoporosis. Conventional oral or intravenous administration of estradiol has many problems, such as, metabolization in gastrointestinal tract and liver, pain by using an injection needle, rapid increase of drug levels in blood and fast clearance with unwanted side effects including thrombosis, endometriosis and uterus carcinoma. The use of nanocarriers for transdermal delivery has been studied because of their ability to deliver therapeutic agents for long time with a controlled ratio, escaping from the first pass effect by liver. In this study, permeability of estradiol-loaded PLGA nanoparticles through rat skin was studied. Higher amount of estradiol was delivered through skin when estradiol was loaded in nanoparticles than estradiol was free molecules. Also, iontophoresis was applied to enhance the permeability of nanoparticles. When iontophoresis was applied, permeability of estradiol-loaded PLGA nanoparticles was much higher than that obtained by simple diffusion of them through skin, since they have negative surface charges. They were found to penetrate through follicles mainly. Also, enhanced permeability effect of estradiol by using nanoparticle system and iontophoresis were observed in vivo. The combination of charged nanoparticle system with iontophoresis is useful for effective transdermal delivery of therapeutic agents.
雌二醇是一种用于治疗围绝经期症状和骨质疏松症的治疗药物。传统的雌二醇口服或静脉给药存在许多问题，例如在胃肠道和肝脏中的代谢、注射针头引起的疼痛、血液中药物水平的快速升高以及快速清除，并伴有包括血栓形成、子宫内膜异位症和子宫癌在内的不良副作用。由于纳米载体能够以可控的比例长时间递送治疗药物，并避免肝脏的首过效应，因此人们对其用于经皮给药进行了研究。在本研究中，对负载雌二醇的聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒通过大鼠皮肤的渗透性进行了研究。当雌二醇负载在纳米颗粒中时，通过皮肤递送的雌二醇量高于游离分子形式的雌二醇。此外，还应用了离子电渗疗法来提高纳米颗粒的渗透性。当应用离子电渗疗法时，负载雌二醇的PLGA纳米颗粒的渗透性远高于其通过皮肤简单扩散所获得的渗透性，因为它们带有负表面电荷。发现它们主要通过毛囊渗透。在体内也观察到了使用纳米颗粒系统和离子电渗疗法增强雌二醇渗透性的效果。带电纳米颗粒系统与离子电渗疗法的结合对于治疗药物的有效经皮递送是有用的。
