a School of Food and Biological Engineering , Hefei University of Technology , Hefei , People's Republic of China.
b Department of Bone Disease and Bone Tumors Surgery , First Affiliated Hospital of Anhui Medical University , Hefei , People's Republic of China.
Drug Deliv. 2019 Dec;26(1):208-215. doi: 10.1080/10717544.2019.1574938.
Cisplatin is the most commonly used antitumor drug in the chemotherapy of a variety of malignancies. However, the severe side effects and drug resistance limit its clinical application. The aim of this study was to develop PLGA-based cisplatin-loaded implants and evaluate the antitumor efficacy of continuous intratumoral chemotherapy with the implants. The cisplatin-loaded implants were prepared by the direct compression method and characterized regarding drug content, micromorphology, in vitro and in vivo drug release profiles. Furthermore, the antitumor activity of the implants was conducted in sarcoma 180 tumor-bearing mice. The SEM images showed smooth surface of the implants and the mean drug content of the tested implants was (37.7% ± 0.5%, w/w). Both in vitro and in vivo release profiles of the implants were characterized by initial burst release followed by the sustained-release of cisplatin. Intratumoral implantation of the cisplatin-loaded implants could effectively inhibit the tumor growth. Additionally, intratumoral chemotherapy with the implants significantly reduced the systemic toxicity compared with intravenous injection of cisplatin. It is worth noting that an increase in the dose of the implants led to a higher tumor suppression rate without additional systemic toxicity. These results demonstrated that cisplatin-loaded implants enhanced the antitumor efficacy and reduced the dose-related side effects in sarcoma 180 tumor-bearing mice.
顺铂是多种恶性肿瘤化疗中最常用的抗肿瘤药物。然而,其严重的副作用和耐药性限制了其临床应用。本研究旨在开发基于 PLGA 的顺铂载药植入物,并评估该植入物进行肿瘤内持续化疗的抗肿瘤疗效。顺铂载药植入物采用直接压缩法制备,并对其药物含量、微观形貌、体外和体内药物释放曲线进行了表征。此外,还在肉瘤 180 荷瘤小鼠中进行了该植入物的抗肿瘤活性研究。SEM 图像显示植入物表面光滑,经测试的植入物的平均药物含量为(37.7%±0.5%,w/w)。植入物的体外和体内释放曲线均表现为初始突释后顺铂的持续释放。顺铂载药植入物的瘤内植入可有效抑制肿瘤生长。此外,与顺铂静脉注射相比,瘤内化疗可显著降低全身毒性。值得注意的是,增加植入物的剂量不会导致额外的全身毒性,却能提高肿瘤抑制率。这些结果表明,顺铂载药植入物增强了肉瘤 180 荷瘤小鼠的抗肿瘤疗效,降低了剂量相关的副作用。