Sonvico Fabio, Barbieri Stefano, Colombo Paolo, Mucchino Claudio, Barocelli Elisabetta, Cantoni Anna Maria, Cavazzoni Andrea, Petronini Pier Giorgio, Rusca Michele, Carbognani Paolo, Ampollini Luca
Biopharmanet-TEC, University of Parma, Parma, Italy.
Department of Food and Drug, University of Parma, Parma, Italy.
J Thorac Dis. 2018 Jan;10(Suppl 2):S194-S206. doi: 10.21037/jtd.2017.10.12.
Malignant mesothelioma is an invasive neoplasm arising from mesothelial surfaces of the pleural and peritoneal cavities. Mesothelioma treatment is unsatisfactory and recurrence is common. Here an innovative locoregional treatment for malignant pleural mesothelioma is presented.
Chitosan- and hyaluronate-based films were loaded with 0.5% and 4% w/w cisplatin and were studied for their physicochemical, mechanical and drug release characteristics. The performance of the drug delivery systems was assessed on A549 cells and on an orthotopic model of MPM recurrence in rats.
Polysaccharide films produced were thin, flexible and resistant. Cisplatin was completely released from hyaluronic acid films within 96 hours, while drug release was found to be much more prolonged with chitosan films. The drug released from hyaluronate films was effective against A549 cell line, while for chitosan films the release was too slow to produce cytotoxicity. Similarly, cisplatin-loaded chitosan films released minimal quantities of cisplatin and induced inflammation and foreign body reaction. Cisplatin-loaded hyaluronate acid films on the contrary were able to prevent tumor recurrence. The cisplatin-loaded hyaluronate films provided higher C and AUC compared to a solution of cisplatin administered intrapleurally, but did not show any sign of treatment related toxicity.
Hyaluronate-based films appear as an optimal platform for the development of drug delivery systems suitable for the loco-regional post-surgical treatment of lung malignancies.
恶性间皮瘤是一种起源于胸膜和腹膜腔间皮表面的侵袭性肿瘤。间皮瘤的治疗效果不尽人意，复发很常见。本文介绍了一种针对恶性胸膜间皮瘤的创新局部治疗方法。
将基于壳聚糖和透明质酸的薄膜负载0.5%和4%（w/w）的顺铂，并研究其物理化学、机械和药物释放特性。在A549细胞和大鼠MPM复发的原位模型上评估药物递送系统的性能。
制备的多糖薄膜薄、柔韧且耐用。顺铂在96小时内从透明质酸薄膜中完全释放，而壳聚糖薄膜的药物释放时间长得多。从透明质酸薄膜释放的药物对A549细胞系有效，而壳聚糖薄膜的释放太慢，无法产生细胞毒性。同样，负载顺铂的壳聚糖薄膜释放的顺铂量极少，并引发炎症和异物反应。相反，负载顺铂的透明质酸薄膜能够预防肿瘤复发。与胸膜腔内注射顺铂溶液相比，负载顺铂的透明质酸薄膜提供了更高的C和AUC，但未显示出任何与治疗相关的毒性迹象。
基于透明质酸的薄膜似乎是开发适合肺恶性肿瘤局部术后治疗的药物递送系统的最佳平台。
