Zhang Yahan, Ma Mengke, Chen Longming, Du Xinbei, Meng Zhao, Zhang Han, Zheng Zhibing, Chen Junyi, Meng Qingbin
State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
Key Laboratory of Inorganic-Organic Hybrid Functional Material Chemistry, Tianjin Key Laboratory of Structure and Performance for Functional Molecules, College of Chemistry, Ministry of Education, Tianjin Normal University, Tianjin 300387, China.
Pharmaceutics. 2022 Nov 28;14(12):2621. doi: 10.3390/pharmaceutics14122621.
Advanced external preparations that possess a sustained-release effect and integrate few irritant elements are urgently needed to satisfy the special requirements of topical administration in the clinic. Here, a series of liquid pillar[n]arene-bearing varying-length oligoethylene oxide chains (OEPns) were designed and synthesized. Following rheological property and biocompatibility investigations, pillar[6]arene with triethylene oxide substituents (TEP6) with satisfactory cavity size were screened as optimal candidate compounds. Then, a supramolecular liquid reservoir was constructed from host-guest complexes between TEP6 and econazole nitrate (ECN), an external antimicrobial agent without additional solvents. In vitro drug-release studies revealed that complexation by TEP6 could regulate the release rate of ECN and afford effective cumulative amounts. In vivo pharmacodynamic studies confirmed the formation of a supramolecular liquid reservoir contributed to the accelerated healing rate of a -infected mouse wound model. Overall, these findings have provided the first insights into the construction of a supramolecular liquid reservoir for topical administration.
迫切需要具有缓释效果且刺激性成分少的先进外用制剂，以满足临床局部给药的特殊要求。在此，设计并合成了一系列带有不同长度聚环氧乙烷链（OEPn）的柱状[n]芳烃。在进行流变学性质和生物相容性研究后，筛选出具有令人满意空腔尺寸的带有三环氧乙烷取代基的柱状[6]芳烃（TEP6）作为最佳候选化合物。然后，由TEP6与外部抗菌剂硝酸益康唑（ECN）之间的主客体络合物构建了一种超分子液体储库，无需额外溶剂。体外药物释放研究表明，TEP6的络合作用可调节ECN的释放速率并提供有效的累积量。体内药效学研究证实，超分子液体储库的形成有助于加速感染小鼠伤口模型的愈合速度。总体而言，这些发现为构建用于局部给药的超分子液体储库提供了初步见解。
