{"title":"构建和评估具有持续释放和增强抗肿瘤效果的 ALK/HDACs 双靶向抑制剂脂质体给药系统。","authors":"Fang Ren, Zongjie Gan, Qianyu Zhang, Dan He, Baoyan Chen, Xianwei Wu, Xiaolin Zeng, Kexin Wu, Yangchen Xing, Yan Zhang, Huali Chen","doi":"10.1007/s13346-024-01647-1","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"939-954"},"PeriodicalIF":5.7000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Construction and evaluation of liposomal drug delivery system for an ALK/HDACs dual-targeted inhibitor with sustained release and enhanced antitumor effect.\",\"authors\":\"Fang Ren, Zongjie Gan, Qianyu Zhang, Dan He, Baoyan Chen, Xianwei Wu, Xiaolin Zeng, Kexin Wu, Yangchen Xing, Yan Zhang, Huali Chen\",\"doi\":\"10.1007/s13346-024-01647-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":11357,\"journal\":{\"name\":\"Drug Delivery and Translational Research\",\"volume\":\" \",\"pages\":\"939-954\"},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2025-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug Delivery and Translational Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s13346-024-01647-1\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/8/7 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Delivery and Translational Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13346-024-01647-1","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/7 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Construction and evaluation of liposomal drug delivery system for an ALK/HDACs dual-targeted inhibitor with sustained release and enhanced antitumor effect.
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.
期刊介绍：
The journal provides a unique forum for scientific publication of high-quality research that is exclusively focused on translational aspects of drug delivery. Rationally developed, effective delivery systems can potentially affect clinical outcome in different disease conditions.
Research focused on the following areas of translational drug delivery research will be considered for publication in the journal.
Designing and developing novel drug delivery systems, with a focus on their application to disease conditions;
Preclinical and clinical data related to drug delivery systems;
Drug distribution, pharmacokinetics, clearance, with drug delivery systems as compared to traditional dosing to demonstrate beneficial outcomes
Short-term and long-term biocompatibility of drug delivery systems, host response;
Biomaterials with growth factors for stem-cell differentiation in regenerative medicine and tissue engineering;
Image-guided drug therapy,
Nanomedicine;
Devices for drug delivery and drug/device combination products.
In addition to original full-length papers, communications, and reviews, the journal includes editorials, reports of future meetings, research highlights, and announcements pertaining to the activities of the Controlled Release Society.
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