Azocalixarenes: a scaffold of universal excipients with high efficiency  

作　　者：Yu-Xin Yue Yi-Lin Lin Meng-Meng Chen Han-Wen Tian Rong Ma Ze-Han Wang Fang-Yuan Chen Yu-Chen Pan Dong-Sheng Guo 

机构地区：[1]College of Chemistry,State Key Laboratory of Elemento-Organic Chemistry,Key Laboratory of Functional Polymer Materials(Ministry of Education),Frontiers Science Center for New Organic Matter,Collaborative Innovation Center of Chemical Science and Engineering(Tianjin),Nankai University,Tianjin 300071,China

出　　处：《Science China Chemistry》2024年第5期1697-1706,共10页中国科学（化学英文版）

基　　金：supported by the National Natural Science Foundation of China (U20A20259, 22201141);the Fundamental Research Funds for the Central Universities;the NCC Fund(NCC2020FH04);the China Postdoctoral Science Foundation(2022M711697)。

摘　　要：Excipients are important components of pharmaceutical preparations that affect their quality, safety, and efficacy. Macrocyclic receptors are a family of supramolecular excipients with several advantages, including molecular-level protection, small sizes,fast kinetics of host-guest recognition, and modular construction. With the continuous advances in the medical field, personalized and precision medicine requires the development of excipients with low dosages, integrated modifying effects, universality,and controlled release. To meet these requirements, we have developed a new family of macrocyclic excipients based on calixarenes by integrating their covalent(broad chemical design space) and noncovalent(wide range of substrates) advantages.Accordingly, azocalixarenes(Azo CAs) were designed, showing high binding affinities to a broad spectrum of active pharmaceutical ingredients(APIs), selectivity to interferents, and responsiveness to hypoxic microenvironments. Due to their highly efficient and controllable recognition, Azo CAs serve as low-dose excipients for 30 APIs. Molecular encapsulation by Azo CAs results in the integrated modification of the physicochemical properties of APIs, including solubility, stability, bioavailability,and biocompatibility. Moreover, Azo CAs can be reduced by azoreductases overexpressed in hypoxic microenvironments,leading to the controlled release of APIs. Collectively, Azo CA excipients have broad application prospects for a series of diseases such as enteritis, arthritis, stroke, cancer, bacterial infection and kidney injury, with diverse therapeutic modalities,including chemotherapy, photodynamic therapy, photothermal therapy, immunotherapy, boron neutron capture therapy, radiotherapy, fluorescence imaging, and their combinations.

关 键 词：supramolecular chemistry host-guest systems EXCIPIENT CALIXARENE molecular recognition 

分 类 号：TQ460.1[化学工程—制药化工]