Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal, India.
J Drug Target. 2011 Feb;19(2):104-13. doi: 10.3109/10611861003733987. Epub 2010 Apr 1.
Specific targeting of tumor cells to achieve higher drug levels in tumor tissue and to overcome the side effects is the major goal in cancer therapy. Nanoparticles encapsulating a hydrophobic core in their nanoreservoir structure were developed as a carrier for a water-insoluble drug, paclitaxel. In the present study, target-oriented nanoparticles based on biodegradable O-carboxymethyl chitosan modified with stearic acid. The surface of the nanoparticles was modified by covalent attachment of folic acid (FA) by simple carbodimide reaction to achieve tumor cell targeting property. Nanoparticles were prepared by the sonication method without involving any surfactants/emulsifiers. The nanoparticles were characterized by various state-of-the-art techniques, including laser light scattering for particles size distribution, field emission scanning electron microscopy and transmission electron microscope for surface morphology. The drug release property and the cytotoxicity of the drug loaded nanoparticles to both cancerous and noncancerous cells were evaluated in cell culture system. To our knowledge, this is the first study demonstrating a FA modified hydrophobically chitosan with paclitaxel-loaded nanoparticles targeting of folate receptor overexpressing cancer cells.
特异性靶向肿瘤细胞以在肿瘤组织中实现更高的药物水平并克服副作用是癌症治疗的主要目标。纳米颗粒在其纳米储库结构中包裹疏水核心,被开发为一种水不溶性药物紫杉醇的载体。在本研究中,基于可生物降解的 O-羧甲基壳聚糖的靶向纳米颗粒,用硬脂酸进行修饰。通过简单的碳二亚胺反应,将叶酸(FA)共价连接到纳米颗粒表面,以实现肿瘤细胞靶向性。纳米颗粒通过超声处理方法制备,不涉及任何表面活性剂/乳化剂。通过各种最先进的技术对纳米颗粒进行了表征,包括用于颗粒尺寸分布的激光光散射、场发射扫描电子显微镜和透射电子显微镜用于表面形态。在细胞培养系统中评估了载药纳米颗粒的药物释放特性和对癌细胞和非癌细胞的细胞毒性。据我们所知,这是第一项研究表明,FA 修饰的疏水性壳聚糖与载有紫杉醇的纳米颗粒能够靶向叶酸受体过表达的癌细胞。