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柚皮素-羟丙基-β-环糊精包合物的表征及其肺部给药的体内外评价。

Characterization, in Vitro and in Vivo Evaluation of Naringenin-Hydroxypropyl-ß-Cyclodextrin Inclusion for Pulmonary Delivery.

机构信息

Guangdong Engineering & Technology Research Center for Quality and Efficacy Reevaluation of Post-Market Traditional Chinese Medicine, Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, No. 135, Xingang Xi Road, Guangzhou 510275, China.

出版信息

Molecules. 2020 Jan 28;25(3):554. doi: 10.3390/molecules25030554.

Abstract

Naringenin, a flavonoid compound which exists abundantly in fruits, is proven to possess excellent antitussive and expectorant effects. However, the clinical applications of naringenin are restricted by its poor solubility and low local concentration by oral administration. The aim of the present study is to prepare a naringenin-hydroxypropyl-β-cyclodextrin (naringenin-HPβCD) inclusion as an inhalation solution for pulmonary delivery. The naringenin-HPβCD inclusion was characterized by phase solubility study, XRD, differential scanning calorimetry (DSC), proton nuclear magnetic resonance (HNMR), and two-dimensional rotating frame Overhauser effect spectroscopy (2D ROESY). The in vitro permeability of the inclusion was evaluated on Calu-3 cells and the pharmacokinetic profile of pulmonary delivery was investigated in Sprague-Dawley (SD) rats. Based on the linear model of phase solubility study, the relationship between naringenin and HPβCD was identified as A type with a 1:1 stoichiometry. XRD, DSC, and NMR studies indicated that the entire naringenin molecule is encapsulated into the cavity of HPβCD. HPβCD could increase the concentration of naringenin in the epithelium-lining fluid (ELF) of Calu-3 cells and act as a sustained release system for naringenin. The pharmacokinetic profile of naringenin-HPβCD inclusion showed rapid response and higher local concentration by pulmonary delivery. In conclusion, pulmonary delivery of naringenin-HPβCD inclusion is a promising formulation strategy, which could provide a new possibility for the clinical application of naringenin.

摘要

柚皮苷是一种广泛存在于水果中的类黄酮化合物,已被证明具有优异的镇咳和平喘作用。然而,柚皮苷的临床应用受到其口服给药时溶解度差和局部浓度低的限制。本研究旨在制备柚皮苷-羟丙基-β-环糊精(柚皮苷-HPβCD)包合物作为肺部给药的吸入溶液。通过相溶解度研究、XRD、差示扫描量热法(DSC)、质子核磁共振(HNMR)和二维旋转框架过氧化物效应光谱(2D ROESY)对柚皮苷-HPβCD 包合物进行了表征。在 Calu-3 细胞上评估了包合物的体外通透性,并在 Sprague-Dawley(SD)大鼠中研究了肺部给药的药代动力学特征。基于相溶解度研究的线性模型,确定了柚皮苷和 HPβCD 之间的关系为 1:1 化学计量比的 A 型。XRD、DSC 和 NMR 研究表明,整个柚皮苷分子被包封在 HPβCD 的腔中。HPβCD 可以增加 Calu-3 细胞上皮衬里液(ELF)中柚皮苷的浓度,并作为柚皮苷的持续释放系统。柚皮苷-HPβCD 包合物的药代动力学特征显示出肺部给药的快速响应和更高的局部浓度。总之,肺部给药柚皮苷-HPβCD 包合物是一种有前途的制剂策略,为柚皮苷的临床应用提供了新的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c0a/7036785/fc89c69c0781/molecules-25-00554-g001.jpg

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