ALK/HDACs双靶点抑制剂（PT-54）是一种基于药效基团融合策略合成的2,4-嘧啶二胺衍生物，可同时抑制间变性淋巴瘤激酶（ALK）和组蛋白脱乙酰酶（HDACs），在治疗多种疾病方面具有显着疗效。癌症。但其水溶性差限制了其临床应用。在本研究中，我们通过膜水合方法制备了PT-54脂质体（PT-54-LPs）来克服这一缺陷。以包封率（EE）和粒径为评价指标，探索PT-54-LPs的制备条件。进一步研究了 PT-54-LP 的形貌、粒径、EE、载药量 (DLC)、药物释放特性和稳定性。体外药物释放研究表明，与游离 PT-54 相比，PT-54-LP 表现出显着的缓释特性。 PT-54-LPs 还表现出比游离 PT-54 更好的肿瘤抑制作用，且没有明显的副作用。这些结果表明PT-54-LPs表现出持续的药物释放并显着提高了PT-54的肿瘤选择性。因此，PT-54-LP 在提高抗癌效率方面显示出巨大的前景。© 2024。控释协会。

ALK/HDACs dual target inhibitor (PT-54) was a 2,4-pyrimidinediamine derivative synthesized based on the pharmacophore merged strategy that inhibits both anaplastic lymphoma kinase (ALK) and histone deacetylases (HDACs), which has demonstrated significant efficacy in treating multiple cancers. However, its poor solubility in water limited its clinical application. In this study, we prepared PT-54 liposomes (PT-54-LPs) by the membrane hydration method to overcome this defect. The encapsulation efficiency (EE) and particle size were used as evaluation indicators to explore the preparation conditions of PT-54-LPs. The morphology, particle size, EE, drug loading content (DLC), drug release properties, and stability of PT-54-LPs were further investigated. In vitro drug release studies showed that PT-54-LPs exhibited significant slow-release properties compared with free PT-54. PT-54-LPs also showed better tumor inhibitory effects than free PT-54 without significant adverse effects. These results suggested that PT-54-LPs displayed sustained drug release and significantly improved the tumor selectivity of PT-54. Thus, PT-54-LPs showed significant promise in enhancing anticancer efficiency.© 2024. Controlled Release Society.