Intrapleural polymeric films containing cisplatin for malignant pleural mesothelioma in a rat tumour model: a preliminary study
Intrapleural polymeric films containing cisplatin for malignant pleural mesothelioma in a rat tumour model: a preliminary study
复制标题
DOI：
10.1016/j.ejcts.2009.08.012
复制
发表时间：
2010-03-01
影响因子：
3.4
通讯作者：
Carbognani, Paolo
中科院分区：
文献类型：
--
作者：
Ampollini, Luca;Sonvico, Fabio;Carbognani, Paolo
目的：本研究的目的是探讨胸膜内聚合膜含顺铂对局部复发的恶性胸膜间皮瘤在大鼠肿瘤模型。方法：采用大鼠恶性胸膜间皮瘤原位复发模型。每组评价5只动物。构建了用于局部递送抗癌药物的聚合物膜（直径4.5 cm）：透明质酸盐、壳聚糖和组合的双层聚合物负载有浓度为100 mg m（-2）的顺铂。没有任何辅助治疗的动物用作对照。间皮瘤细胞胸膜下注射麻醉大鼠。六天后，胸膜炎。切除5.5mm的肿瘤，并进行左肺切除术和胸膜磨损。此后，根据随机分组，胸膜内应用顺铂负载和未负载薄膜或顺铂溶液。6天后，对动物实施安乐死并收获器官用于形态学和组织学评价。主要终点是肿瘤复发的体积。次要终点是治疗相关毒性;在不同时间点评价的顺铂血清浓度;和尸检时测量的胸膜中的顺铂浓度。采用方差分析（ANOVA）进行统计分析。采用Bonferroni校正进行所有组之间的比较。结果如下：与对照组相比，透明质酸盐顺铂和透明质酸盐-壳聚糖顺铂组的肿瘤体积显著减小（分别为p = 0.001和p < 0.0001）。用透明质酸盐-壳聚糖顺铂治疗的动物的肿瘤复发显著低于用顺铂溶液（p = 0.003）和透明质酸盐顺铂（p = 0.032）治疗的动物。未观察到与不同处理相关的毒性。在术后第1天和第2天，在血清中检测到顺铂，与顺铂溶液相比，透明质酸盐顺铂和透明质酸盐-壳聚糖顺铂组的顺铂浓度显著高出6倍和7倍，并且随着时间的推移而维持。透明质酸-壳聚糖顺铂组胸膜中的顺铂水平高于所有其他组。结论：与顺铂溶液相比，透明质酸钠-壳聚糖顺铂在减少肿瘤复发方面具有显著效果。透明质酸和透明质酸-壳聚糖负载顺铂确保了比顺铂溶液更高和更长的血浆药物浓度，而不增加毒性。(C)2009年欧洲胸外科协会。Elsevier B. V.出版，保留所有权利。
Objective: This study aims to investigate the effect of intrapleural polymeric films containing cisplatin on the local recurrence of malignant pleural mesothelioma in a rat tumour model. Methods: An orthotopic rat recurrence model of malignant pleural mesothelioma was used. Five animals per group were evaluated. Polymeric films (4.5 cm diameter) for the local delivery of anticancer drug were constructed: hyaluronate, chitosan and the combined dual-layer polymers were loaded with cisplatin at a concentration of 100 mg m(-2). Animals without any adjuvant therapy were used as control. Mesothelioma cells were injected subpleurally in the anaesthetised rats. Six days later, a pleural. tumour of 5.5 mm was resected and a left pneumonectomy and pleural abrasion were performed. Thereafter, the cisplatin-loaded and unloaded films or cisplatin solution were intrapleurally applied, according to randomisation. After 6 days, animals were euthanised and organs harvested for morphological and histological evaluations. The primary endpoint was the volume of tumour recurrence. The secondary endpoints were treatment-related toxicity; cisplatin serum concentration evaluated at different time points; and cisplatin concentration in the pleura measured at autopsy. Analysis of variance (ANOVA) was used for statistical analysis. Bonferroni correction was applied for comparison between all groups. Results: Tumour volume was significantly reduced in the hyaluronate cisplatin and hyaluronate-chitosan cisplatin groups in comparison to control groups (p = 0.001 and p < 0.0001, respectively). Animals treated with hyaluronate-chitosan cisplatin had a tumour recurrence significantly lesser than animals treated with cisplatin solution (p = 0.003) and hyaluronate cisplatin (p = 0.032). No toxicity related to the different treatments was observed. On postoperative days 1 and 2, cisplatin was detected in the serum at a concentration six- and sevenfold significantly higher in the hyaluronate cisplatin and hyaluronate-chitosan cisplatin groups, in comparison to cisplatin solution, and was maintained over time. Cisplatin levels in the pleura were higher in the hyaluronate-chitosan cisplatin group than in all others. Conclusions: Hyaluronate-chitosan cisplatin was significantly effective in reducing tumour recurrence compared with cisplatin solution. Hyaluronate and hyaluronate-chitosan loaded with cisplatin assured significantly higher and more prolonged plasmatic drug concentrations than cisplatin solution without increasing toxicity. (C) 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.