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蜂蜜及蜂蜜基药物制剂中酚酸的体外皮肤渗透和蓄积评估

Assessment of in vitro skin permeation and accumulation of phenolic acids from honey and honey-based pharmaceutical formulations.

作者信息

Nowak Anna, Muzykiewicz-Szymańska Anna, Perużyńska Magdalena, Kucharska Edyta, Kucharski Łukasz, Jakubczyk Karolina, Niedźwiedzka-Rystwej Paulina, Stefanowicz-Hajduk Justyna, Droździk Marek, Majtan Juraj

机构信息

Department of Cosmetic and Pharmaceutical Chemistry, Pomeranian Medical University in Szczecin, 72 Powstancow Wlkp. Ave, Szczecin, 70-111, Poland.

Department of Experimental and Clinical Pharmacology, Pomeranian Medical University in Szczecin, 72 Powstancow Wlkp. Ave, Szczecin, 70-111, Poland.

出版信息

BMC Complement Med Ther. 2025 Feb 4;25(1):43. doi: 10.1186/s12906-025-04786-1.

Abstract

BACKGROUND

Honey has been successfully used in wound care and cosmetics because of its effective biological properties, including antibacterial, antioxidant, and anti-inflammatory activities. Polyphenols, particularly phenolic acids, are key honey components responsible for these beneficial effects. In recent years, there has been a growing demand for natural, ecologically friendly, and biodegradable products in the modern cosmetics and wound care market. This study aimed to identify and quantify phenolic acids in four Polish honey samples of different botanical origins (heather, buckwheat, linden and rapeseed) and to assess for the first time the permeation of the identified phenolic acids through the skin and their accumulation after the application of pure honey samples, as well as honey-based hydrogel and emulsion formulations.

METHODS

The honey samples' antioxidant activity and total phenolic content were determined using the DPPH and ABTS assays and the Folin-Ciocalteu method, respectively. Phenolic acids and volatile compounds were identified and quantified in honey samples using the HPLC-UV and GC-MS method, respectively. The biocompatibility of the honey samples was evaluated using a murine fibroblast cell line (L929). A Franz-type vertical diffusion cell with porcine skin was used to assess phenolic acid's permeation and skin accumulation from different honey-based pharmaceutical formulations. The biodegradability of the prepared formulations was also characterised.

RESULTS

Gallic acid, 3,4-dihydroxybenzoic acid, 2,5-dihydroxybenzoic acid, coumaric acid, and 3-hydroxybenzoic acid were identified and quantified in the honey samples. Heather honey exhibited significantly higher antioxidant activity and total polyphenol content than the other honey samples. Heather, linden and buckwheat honey samples significantly decreased cell viability at concentrations of 5% and 2.5%, while rapeseed honey sample markedly reduced fibroblast viability only at 5%. Among the tested formulations - pure honey, hydrogel, and emulsion - higher skin permeation and accumulation rates of phenolic acids were observed with the prepared honey-based hydrogels than with the pure honeys and emulsions. Additionally, the prepared formulations were classified as partially biodegradable.

CONCLUSIONS

The obtained results confirmed the effectiveness of two pharmaceutical formulations in the form of a hydrogel or emulsion containing honey after applied topically. The inclusion of honey in the vehicle, in particular hydrogel increased the penetration of phenolic acids through the skin.

摘要

背景

蜂蜜因其有效的生物学特性,包括抗菌、抗氧化和抗炎活性,已成功应用于伤口护理和化妆品领域。多酚,尤其是酚酸,是赋予蜂蜜这些有益功效的关键成分。近年来,现代化妆品和伤口护理市场对天然、生态友好且可生物降解产品的需求不断增长。本研究旨在鉴定和定量分析四种不同植物来源(石南、荞麦、椴树和油菜籽)的波兰蜂蜜样品中的酚酸,并首次评估所鉴定的酚酸透过皮肤的渗透率以及在涂抹纯蜂蜜样品、蜂蜜基水凝胶和乳液制剂后的蓄积情况。

方法

分别采用DPPH和ABTS法以及福林 - 酚法测定蜂蜜样品的抗氧化活性和总酚含量。分别使用HPLC - UV和GC - MS法鉴定和定量分析蜂蜜样品中的酚酸和挥发性化合物。使用小鼠成纤维细胞系(L929)评估蜂蜜样品的生物相容性。采用带有猪皮的弗兰兹型垂直扩散池评估不同蜂蜜基药物制剂中酚酸的渗透和皮肤蓄积情况。还对所制备制剂的生物降解性进行了表征。

结果

在蜂蜜样品中鉴定并定量分析出了没食子酸、3,4 - 二羟基苯甲酸、2,5 - 二羟基苯甲酸、香豆酸和3 - 羟基苯甲酸。石南蜂蜜的抗氧化活性和总多酚含量显著高于其他蜂蜜样品。石南、椴树和荞麦蜂蜜样品在浓度为5%和2.5%时显著降低细胞活力,而油菜籽蜂蜜样品仅在5%时显著降低成纤维细胞活力。在所测试的制剂——纯蜂蜜、水凝胶和乳液中,与纯蜂蜜和乳液相比,所制备的蜂蜜基水凝胶中酚酸的皮肤渗透率和蓄积率更高。此外,所制备的制剂被归类为部分可生物降解。

结论

所得结果证实了局部应用含蜂蜜的水凝胶或乳液形式的两种药物制剂的有效性。将蜂蜜添加到载体中,特别是水凝胶中,可增加酚酸透过皮肤的渗透率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cae/11796271/5ab1b4facee5/12906_2025_4786_Fig1_HTML.jpg

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