Université Paris Cité, CNRS, Inserm, UTCBS, F-75006, Paris, France; Pharmacy Department, AP-HP, Henri Mondor Hospital Group, F-94010, France.
Université Paris Cité, CNRS, Inserm, UTCBS, F-75006, Paris, France.
Int J Pharm. 2024 Feb 15;651:123744. doi: 10.1016/j.ijpharm.2023.123744. Epub 2023 Dec 23.
Lung cancer is a highly vascularized tumor for which a combination between an antitumor agent, cisplatin, and an antiangiogenic molecule, fisetin, appears a promising therapeutic approach. In order to deliver both chemotherapies within the tumor, to enhance fisetin solubility and decrease cisplatin toxicity, an encapsulation of both drugs into liposomes was developed. Purification and freeze-drying protocols were optimized to improve both the encapsulation and liposome storage. The cytotoxicity of the encapsulated chemotherapies was evaluated on Lewis lung carcinoma (3LL) cell lines. The antitumor effect of the combination was evaluated in vivo on an ectopic mouse model of Lewis Lung carcinoma. The results showed that fisetin and cisplatin co-loaded liposomes were successfully prepared. Freeze-drying allowed a 30 days storage limiting the release of both drugs. The combination index between liposomal fisetin and liposomal cisplatin on 3LL cell line after 24 h of exposure showed a clear synergism: CI = 0.7 for the co loaded liposomes and CI = 0.9 for the mixture of cisplatin loaded and fisetin loaded liposomes. The co-encapsulating formulation showed in vivo efficacy against an ectopic murine model of Lewis Lung carcinoma with a probable reduction in the toxicity of cisplatin through co-encapsulation with fisetin.
肺癌是一种高度血管化的肿瘤，联合使用抗肿瘤药物顺铂和抗血管生成分子非瑟酮似乎是一种很有前途的治疗方法。为了在肿瘤内同时输送两种化疗药物，提高非瑟酮的溶解度并降低顺铂的毒性，将这两种药物包封在脂质体中。优化了纯化和冷冻干燥方案，以提高包封率和脂质体的储存稳定性。评估了包封化疗药物对 Lewis 肺癌（3LL）细胞系的细胞毒性。在 Lewis 肺癌的异位小鼠模型中评估了联合治疗的抗肿瘤作用。结果表明，成功制备了非瑟酮和顺铂共载脂质体。冷冻干燥允许储存 30 天，限制了两种药物的释放。在暴露 24 小时后，3LL 细胞系上载有非瑟酮和载有顺铂的脂质体的组合指数显示出明显的协同作用：共载脂质体的 CI 为 0.7，载有顺铂和载有非瑟酮的脂质体混合物的 CI 为 0.9。共包封制剂对 Lewis 肺癌异位小鼠模型具有体内疗效，可能通过与非瑟酮共包封降低了顺铂的毒性。
