The improved antitumor efficacy of continuous intratumoral chemotherapy with cisplatin-loaded implants for the treatment of sarcoma 180 tumor-bearing mice

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（Cisplatin）是多种恶性肿瘤化疗中最常用的抗肿瘤药物，但其严重的不良反应与耐药性限制了临床应用。本研究旨在开发基于聚乳酸-羟基乙酸共聚物（PLGA）的载顺铂植入剂，并评价该植入剂实施持续瘤内化疗的抗肿瘤效果。采用直接压片法制备载顺铂植入剂，并对其药物含量、微观形貌、体外及体内药物释放特征进行表征。此外，在肉瘤180荷瘤小鼠模型中考察了该植入剂的抗肿瘤活性。扫描电子显微镜（SEM）结果显示，植入剂表面光滑，受试植入剂的平均药物含量为(37.7% ± 0.5%，w/w)。该植入剂的体外与体内释放曲线均呈现初始突释后伴随顺铂持续缓释的特征。瘤内植入载顺铂植入剂可有效抑制肿瘤生长。与静脉注射顺铂相比，采用该植入剂进行瘤内化疗可显著降低全身毒性。值得注意的是，提高植入剂剂量可提升肿瘤抑制率，且未产生额外的全身毒性。上述结果表明，在肉瘤180荷瘤小鼠中，载顺铂植入剂可增强抗肿瘤效果并降低剂量相关不良反应。