Tomoda Keishiro, Ohkoshi Takumi, Hirota Keiji, Sonavane Ganeshchandra S, Nakajima Takehisa, Terada Hiroshi, Komuro Masahito, Kitazato Kenji, Makino Kimiko
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
Colloids Surf B Biointerfaces. 2009 Jul 1;71(2):177-82. doi: 10.1016/j.colsurfb.2009.02.001. Epub 2009 Feb 11.
Nanoparticles have widely been studied in drug delivery research for targeting and controlled release. The aim of this article is application of nanoparticles as an inhalable agent for treatment of lung cancer. To deposit effectively deep the particles in the lungs, the PLGA nanoparticles loaded with the anticancer drug 6-{[2-(dimethylamino)ethyl]amino}-3-hydroxyl-7H-indeno[2,1-c]quinolin-7-one dihydrochloride (TAS-103) were prepared in the form of nanocomposite particles. The nanocomposite particles consist of the complex of drug-loaded nanoparticles and excipients. In this study, the anticancer effects of the nanocomposite particles against the lung cancer cell line A549. Also, the concentration of TAS-103 in blood and lungs were determined after administration of the nanocomposite particles by inhalation to rats. TAS-103-loaded PLGA nanoparticles were prepared with 5% and 10% of loading ratio by spray drying method with trehalose as an excipient. The 5% drug-loaded nanocomposite particles were more suitable for inhalable agent because of the sustained release of TAS-103 and higher FPF value. Cytotoxicity of nanocomposite particles against A549 cells was higher than that of free drug. When the nanocomposite particles were administered in rats by inhalation, drug concentration in lung was much higher than that in plasma. Furthermore, drug concentration in lungs administered by inhalation of nanocomposite particles was much higher than that after intravenous administration of free drug. From these results, the nanocomposite particle systems could be promising for treatment of lung cancer.
纳米颗粒在靶向和控释给药研究中已得到广泛研究。本文的目的是将纳米颗粒用作治疗肺癌的吸入剂。为了使颗粒有效地沉积在肺部深处，制备了负载抗癌药物6-{[2-(二甲氨基)乙基]氨基}-3-羟基-7H-茚并[2,1-c]喹啉-7-酮二盐酸盐（TAS-103）的PLGA纳米颗粒，呈纳米复合颗粒形式。纳米复合颗粒由载药纳米颗粒与辅料的复合物组成。在本研究中，研究了纳米复合颗粒对肺癌细胞系A549的抗癌作用。此外，在对大鼠吸入纳米复合颗粒后，测定了血液和肺部中TAS-103的浓度。以海藻糖为辅料，通过喷雾干燥法制备了负载率为5%和10%的载TAS-103的PLGA纳米颗粒。5%载药纳米复合颗粒由于TAS-103的缓释和较高的细粒子分数（FPF）值，更适合作为吸入剂。纳米复合颗粒对A549细胞的细胞毒性高于游离药物。当纳米复合颗粒经吸入给予大鼠时，肺部的药物浓度远高于血浆中的药物浓度。此外，吸入纳米复合颗粒后肺部的药物浓度远高于静脉注射游离药物后的浓度。从这些结果来看，纳米复合颗粒系统在治疗肺癌方面可能具有前景。
