载有 5-氟尿嘧啶的 PEG 水凝胶的药代动力学特性和抗肿瘤疗效。
Pharmacokinetic properties and antitumor efficacy of the 5-fluorouracil loaded PEG-hydrogel.
机构信息
Department of Veterinary Pharmacology and Toxicology, Konkuk University, Seoul 143-701, Republic of Korea.
出版信息
BMC Cancer. 2010 May 18;10:211. doi: 10.1186/1471-2407-10-211.
BACKGROUND
We have studied the in vitro and in vivo utility of polyethylene glycol (PEG)-hydrogels for the development of an anticancer drug 5-fluorouracil (5-FU) delivery system.
METHODS
A 5-FU-loaded PEG-hydrogel was implanted subcutaneously to evaluate the drug retention time and the anticancer effect. For the pharmacokinetic study, two groups of male rats were administered either an aqueous solution of 5-FU (control group)/or a 5-FU-loaded PEG-hydrogel (treated group) at a dose of 100 mg/kg. For the pharmacodynamic study, a human non-small-cell lung adenocarcinoma (NSCLC) cell line, A549 was inoculated to male nude mice with a cell density of 3 x 10(6). Once tumors start growing, the mice were injected with 5-FU/or 5-FU-loaded PEG-hydrogel once a week for 4 weeks. The growth of the tumors was monitored by measuring the tumor volume and calculating the tumor inhibition rate (IR) over the duration of the study.
RESULTS
In the pharmacokinetic study, the 5-FU-loaded PEG-hydrogel gave a mean residence time (MRT) of 8.0 h and the elimination half-life of 0.9 h; these values were 14- and 6-fold, respectively, longer than those for the free solution of 5-FU (p < 0.05). In the pharmacodynamic study, A549 tumor growth was significantly inhibited in the 5-FU-loaded PEG-hydrogel group in comparison to the untreated group beginning on Day 14 (p < 0.05-0.01). Moreover, the 5-FU-loaded PEG-hydrogel group had a significantly enhanced tumor IR (p < 0.05) compared to the free 5-FU drug treatment group.
CONCLUSION
We suggest that 5-FU-loaded PEG-hydrogels could provide a useful tool for the development of an anticancer drug delivery system.
背景
我们研究了聚乙二醇（PEG）水凝胶在开发抗癌药物 5-氟尿嘧啶（5-FU）递药系统中的体外和体内应用。
方法
将载有 5-FU 的 PEG 水凝胶皮下植入以评估药物保留时间和抗癌效果。为了进行药代动力学研究，将两组雄性大鼠分别以 100mg/kg 的剂量给予 5-FU 的水溶液（对照组）/或载有 5-FU 的 PEG 水凝胶（治疗组）。为了进行药效学研究，将人非小细胞肺癌（NSCLC）细胞系 A549 以 3×10(6)的细胞密度接种到雄性裸鼠中。一旦肿瘤开始生长，每周向小鼠注射一次 5-FU/或载有 5-FU 的 PEG 水凝胶，共 4 周。通过测量肿瘤体积并计算研究期间的肿瘤抑制率（IR）来监测肿瘤的生长。
结果
在药代动力学研究中，载有 5-FU 的 PEG 水凝胶的平均驻留时间（MRT）为 8.0 小时，消除半衰期为 0.9 小时；这些值分别是游离 5-FU 溶液的 14 倍和 6 倍（p<0.05）。在药效学研究中，与未治疗组相比，载有 5-FU 的 PEG 水凝胶组从第 14 天开始 A549 肿瘤生长明显受到抑制（p<0.05-0.01）。此外，载有 5-FU 的 PEG 水凝胶组的肿瘤 IR 明显高于游离 5-FU 药物治疗组（p<0.05）。
结论
我们建议载有 5-FU 的 PEG 水凝胶可为开发抗癌药物递药系统提供有用的工具。
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