Cyclodextrin effects on the distribution, solubility and transport properties of umifenovir

IF 4.9 2区化学 Q2 CHEMISTRY, PHYSICAL Colloids and Surfaces A: Physicochemical and Engineering Aspects Pub Date : 2024-10-17 DOI:10.1016/j.colsurfa.2024.135574

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Abstract

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.

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环糊精对乌米诺韦分布、溶解性和运输特性的影响

本研究的起因是对抗病毒药物和潜在的抗 SARS-CoV-2 药物乌米诺韦（UMF）疗效的模糊看法。很有可能，UMF 药效低的原因是其溶解性差，因此口服后生物利用率低。我们的研究旨在利用环糊精改善 UMF 的溶解度及其与分布（1-辛醇/缓冲液和正己烷/缓冲液系统）和渗透性（仿生 PermeaPad 屏障）的相关性。实验表明，UMF 的溶解度和分布参数与水介质的 pH 值密切相关。在缓冲 pH 值为 7.4 的 HP-β-CD 和 SBE-β-CD 溶液中，UMF 的溶解度最大分别提高了 11.2 倍和 29.5 倍。通过在缓冲相中添加多种浓度的 CD 进行分布测试，可以确定分布系数的固有值--这是评估化合物亲油性的重要参数。渗透性与分布之间的相互作用表明，渗透性主要受 UMF 的高亲脂性影响。

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来源期刊

Colloids and Surfaces A: Physicochemical and Engineering Aspects 化学-物理化学

CiteScore

8.70

自引率

9.60%

发文量

2421

审稿时长

56 days

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.