The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Biomaterials. 2012 Jun;33(18):4752-61. doi: 10.1016/j.biomaterials.2012.03.023. Epub 2012 Apr 1.
Colorectal cancer is a significant source of morbidity and mortality in the United States and other Western countries. Oral delivery of therapeutics remains the most patient accepted form of medication. The development of an oral delivery formulation for local delivery of chemotherapeutics in the gastrointestinal tract can potentially alleviate the adverse side effects including systemic cytotoxicity, as well as focus therapy to the lesions. Here we develop an oral formulation of the chemotherapeutic drug oxaliplatin for the treatment of colorectal cancer. Oxaliplatin was encapsulated in pH sensitive, mucoadhesive chitosan-coated alginate microspheres. The microparticles were formulated to release the chemotherapeutics after passing through the acidic gastric environment thus targeting the intestinal tract. In vivo, these particles substantially reduced the tumor burden in an orthotopic mouse model of colorectal cancer, and reduced mortality.
结直肠癌是美国和其他西方国家发病率和死亡率的重要来源。治疗药物的口服给药仍然是最受患者接受的药物形式。开发一种用于胃肠道局部递送化疗药物的口服递药制剂，有可能减轻包括全身细胞毒性在内的不良反应，并将治疗集中在病变部位。在这里，我们开发了一种用于治疗结直肠癌的化疗药物奥沙利铂的口服制剂。奥沙利铂被包封在 pH 敏感的、具有粘膜粘附性的壳聚糖包被的海藻酸钠微球中。这些微球被设计成在通过酸性胃环境后释放化疗药物，从而靶向肠道。在体内，这些颗粒在结直肠原位小鼠模型中显著降低了肿瘤负担，并降低了死亡率。
