Xie Ming, Zhou Liang, Hu Tao, Yao Ming
Department of Otolaryngology, Eye and ENT Hospital, FuDan University, Shanghai, China.
Anticancer Drugs. 2007 Apr;18(4):459-66. doi: 10.1097/CAD.0b013e328012bccd.
The introduction of induction chemotherapy provides an expectation of laryngeal function preservation without reduction in survival for patients with advanced laryngeal squamous cell carcinoma. The antitumor activity of conventional intravenous chemotherapy, however, is limited by systemic toxicity. The polymeric drug system delivered locally provides a novel modality of increasing therapeutic concentrations of drug for a prolonged period while decreasing systemic levels. In the current study, paclitaxel-loaded sustained-release microspheres were developed using poly(lactic-co-glycolic acid) as a drug carrier. Intratumoral administration of paclitaxel in the formulation of polymer showed enhanced efficacy against laryngeal squamous cell carcinoma in nude mice compared with conventional paclitaxel injection via the intratumoral or intraperitoneal route. No significant toxic reactions were observed in the experiment. Immunohistochemical findings indicated that paclitaxel exhibited antiangiogenic activity by inhibiting the expression of basic fibroblast growth factor and vascular endothelial growth factor within the tumor. Moreover, this effect could be better exploited via localized delivery of polymeric paclitaxel. In conclusion, direct administration of polymeric drug system at the tumor sites proved to be promising for the treatment of laryngeal carcinoma.
诱导化疗的引入为晚期喉鳞状细胞癌患者带来了保留喉功能且不降低生存率的期望。然而，传统静脉化疗的抗肿瘤活性受到全身毒性的限制。局部递送的聚合物药物系统提供了一种新的模式，可在延长时间内提高药物治疗浓度，同时降低全身药物水平。在本研究中，以聚乳酸-羟基乙酸共聚物为药物载体，研制了载紫杉醇缓释微球。与通过瘤内或腹腔途径注射传统紫杉醇相比，瘤内注射聚合物剂型的紫杉醇对裸鼠喉鳞状细胞癌显示出更强的疗效。实验中未观察到明显的毒性反应。免疫组化结果表明，紫杉醇通过抑制肿瘤内碱性成纤维细胞生长因子和血管内皮生长因子的表达而表现出抗血管生成活性。此外，通过聚合物紫杉醇的局部递送可以更好地发挥这种作用。总之，在肿瘤部位直接给药聚合物药物系统被证明对喉癌治疗具有前景。
