Chinese PLA General Hospital, Beijing.
Anticancer Drugs. 2010 Jul;21(6):600-8. doi: 10.1097/cad.0b013e3283393004.
The aim was to develop a slow-release poly-lactic-coglycolic acid (PLGA)-oxaliplatin microsphere and to assess the therapeutic effectiveness and safety of this preparation on colorectal tumor in vivo. The PLGA-oxaliplatin microsphere was prepared based on a spray-drying method, and the drug loading and in-vitro oxaliplatin release profile were carried out using high performance liquid chromatography. The inhibiting effect on tumor growth was examined using in-vivo subcutaneously inoculated colorectal tumor models of nude mice. The size of the microsphere was less than 100 microm, drug loading was 18-22% and drug release time lasted as long as 30 days. PLGA-oxaliplatin microspheres significantly restrained tumor growth and this effect correlated with decreased expression of proliferating cell nuclear antigen and increased expression of terminal deoxynucleotidyltransferase dUTP nick end labeling in tumor cells. Bodyweight measurement and blood analysis did not suggest significant adverse effects on the mice during the study. The PLGA-oxaliplatin microsphere developed here was suitable for regional use; it appears safe and effective in controlling the tumor growth. This preparation shows promise in reducing local recurrence of colorectal cancer after resection, but needs further investigation.
目的是研制一种聚乳酸-羟基乙酸（PLGA）-奥沙利铂缓释微球，并评估其在体内结直肠肿瘤中的治疗效果和安全性。采用喷雾干燥法制备 PLGA-奥沙利铂微球，采用高效液相色谱法进行载药量和体外奥沙利铂释放曲线测定。采用裸鼠皮下接种结直肠肿瘤模型进行体内抑瘤作用研究。微球粒径小于 100μm，载药量为 18%-22%，药物释放时间长达 30 天。PLGA-奥沙利铂微球能显著抑制肿瘤生长，这种作用与肿瘤细胞增殖细胞核抗原表达减少和末端脱氧核苷酸转移酶 dUTP 缺口末端标记表达增加有关。在研究过程中，体重测量和血液分析并未提示对小鼠有明显的不良影响。本研究中研制的 PLGA-奥沙利铂微球适合局部应用，在控制肿瘤生长方面安全有效。该制剂有望降低结直肠癌切除术后局部复发的风险，但需要进一步研究。
