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环糊精纳米海绵的制备及对有机有毒分子的去除性能研究。

Preparation and characterization of cyclodextrin nanosponges for organic toxic molecule removal.

机构信息

Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey.

Department of Chemistry, University of Torino, Via P Guiria 7, 10125 Torino, Italy.

出版信息

Int J Pharm. 2020 Jul 30;585:119485. doi: 10.1016/j.ijpharm.2020.119485. Epub 2020 Jun 1.

Abstract

Cyclodextrin-based nanosponges (CD-NS) are considered as safe and biocompatible systems for removing toxic molecules from the body. Rapid removal of toxic molecules that are formed in the body from certain food constituents, is relevant especially for patients affected by chronic kidney disease. Within the scope of this study, innovative cyclodextrin polymers were synthesized to form nanosponges able to remove indole, before it could form the toxic indoxyl sulfate in the body. Furthermore, in vivo studies were carried out using the two optimal CD-NS formulations by assessing physicochemical properties, stability, indole adsorption capacity and in vitro cytotoxicity. NS prepared from β-cyclodextrin cross-linked with toluene diisocyanate was found to be the most effective NS with an in vitro indole adsorption capacity of over 90%. In addition, this derivative was more stable in gastrointestinal media. Animal studies further revealed that oral CD-NSs did not tend to accumulate and damage gastrointestinal tissues and are excreted from the GI tract with minimal absorption. In conclusion, this study suggests that CD-NS formulations are effective and safe in removing toxic molecules from the body. Their potential use in veterinary or human medicine could reduce dialysis frequency and avoid hepatic and cardiac toxicity avoiding the indole formation.

摘要

环糊精纳米海绵(CD-NS)被认为是一种安全且生物相容的系统,可用于从体内去除有毒分子。从某些食物成分中快速去除体内形成的有毒分子,对于患有慢性肾病的患者尤为重要。在本研究范围内,合成了创新的环糊精聚合物,以形成纳米海绵,能够在体内形成有毒的吲哚硫酸之前去除吲哚。此外,通过评估理化性质、稳定性、吲哚吸附能力和体外细胞毒性,使用两种最佳的 CD-NS 制剂进行了体内研究。用甲苯二异氰酸酯交联的β-环糊精制备的 NS 被发现是最有效的 NS,其体外吲哚吸附能力超过 90%。此外,该衍生物在胃肠道介质中更稳定。动物研究进一步表明,口服 CD-NS 不易在胃肠道组织中积累和损伤,并且随粪便排出体外,吸收极少。总之,本研究表明 CD-NS 制剂可有效、安全地从体内去除有毒分子。它们在兽医或人类医学中的潜在用途可能会降低透析频率,避免肝和心脏毒性,避免吲哚的形成。

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