{"title":"环糊精对乌米诺韦分布、溶解性和运输特性的影响","authors":"","doi":"10.1016/j.colsurfa.2024.135574","DOIUrl":null,"url":null,"abstract":"<div><div>The present study was initiated by an ambiguous opinion on the therapeutic efficacy of antiviral and potential anti-SARS-CoV-2 drug umifenovir (UMF). With a high degree of probability, low efficacy of UMF can be due to its poor solubility and, as follows, inefficient bioavailability after oral administration. In our investigation we aimed at improving the UMF solubility with cyclodextrins and its correlation to distribution (1-octanol/buffer and n-hexane/buffer systems) and permeability (biomimetic PermeaPad barrier). The experiments demonstrated a strong dependence of the UMF solubility and distribution parameters on the pH of the aqueous medium. The solubility of UMF was maximally increased up to 11.2-fold and 29.5-fold in HP-β-CD and SBE-β-CD solutions, respectively, with buffer pH 7.4. The distribution tests with the additions of several CDs concentrations to the buffer phase allowed to determine the intrinsic value of the distribution coefficient - the parameter important for the evaluation of the compound lipophilicity. The permeability-distribution interplay demonstrated the permeability to be mainly governed by the high lipophilicity of UMF.</div></div>","PeriodicalId":278,"journal":{"name":"Colloids and Surfaces A: Physicochemical and Engineering Aspects","volume":null,"pages":null},"PeriodicalIF":4.9000,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cyclodextrin effects on the distribution, solubility and transport properties of umifenovir\",\"authors\":\"\",\"doi\":\"10.1016/j.colsurfa.2024.135574\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>The present study was initiated by an ambiguous opinion on the therapeutic efficacy of antiviral and potential anti-SARS-CoV-2 drug umifenovir (UMF). With a high degree of probability, low efficacy of UMF can be due to its poor solubility and, as follows, inefficient bioavailability after oral administration. In our investigation we aimed at improving the UMF solubility with cyclodextrins and its correlation to distribution (1-octanol/buffer and n-hexane/buffer systems) and permeability (biomimetic PermeaPad barrier). The experiments demonstrated a strong dependence of the UMF solubility and distribution parameters on the pH of the aqueous medium. The solubility of UMF was maximally increased up to 11.2-fold and 29.5-fold in HP-β-CD and SBE-β-CD solutions, respectively, with buffer pH 7.4. The distribution tests with the additions of several CDs concentrations to the buffer phase allowed to determine the intrinsic value of the distribution coefficient - the parameter important for the evaluation of the compound lipophilicity. The permeability-distribution interplay demonstrated the permeability to be mainly governed by the high lipophilicity of UMF.</div></div>\",\"PeriodicalId\":278,\"journal\":{\"name\":\"Colloids and Surfaces A: Physicochemical and Engineering Aspects\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.9000,\"publicationDate\":\"2024-10-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Colloids and Surfaces A: Physicochemical and Engineering Aspects\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0927775724024385\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, PHYSICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Colloids and Surfaces A: Physicochemical and Engineering Aspects","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0927775724024385","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
Cyclodextrin effects on the distribution, solubility and transport properties of umifenovir
The present study was initiated by an ambiguous opinion on the therapeutic efficacy of antiviral and potential anti-SARS-CoV-2 drug umifenovir (UMF). With a high degree of probability, low efficacy of UMF can be due to its poor solubility and, as follows, inefficient bioavailability after oral administration. In our investigation we aimed at improving the UMF solubility with cyclodextrins and its correlation to distribution (1-octanol/buffer and n-hexane/buffer systems) and permeability (biomimetic PermeaPad barrier). The experiments demonstrated a strong dependence of the UMF solubility and distribution parameters on the pH of the aqueous medium. The solubility of UMF was maximally increased up to 11.2-fold and 29.5-fold in HP-β-CD and SBE-β-CD solutions, respectively, with buffer pH 7.4. The distribution tests with the additions of several CDs concentrations to the buffer phase allowed to determine the intrinsic value of the distribution coefficient - the parameter important for the evaluation of the compound lipophilicity. The permeability-distribution interplay demonstrated the permeability to be mainly governed by the high lipophilicity of UMF.
期刊介绍:
Colloids and Surfaces A: Physicochemical and Engineering Aspects is an international journal devoted to the science underlying applications of colloids and interfacial phenomena.
The journal aims at publishing high quality research papers featuring new materials or new insights into the role of colloid and interface science in (for example) food, energy, minerals processing, pharmaceuticals or the environment.