氧化白藜芦醇自微乳的制备、表征及美白活性的研究

doi:10.3969/j.issn.2097-2806.2025.04.007

摘要/Abstract

摘要：

以聚氧乙烯蓖麻油和辛酸癸酸聚乙二醇甘油酯为复合乳化剂制备可高效荷载氧化白藜芦醇（OXY）的自微乳递送系统（OXY-SME），表征其制剂特性，并评价其稳定性、体外透皮效果和美白活性。通过伪三元相图及乳液的粒径和多分散指数（PDI），明确了空白自微乳（SME）的制备处方和OXY的最适载药量。在最适载药量为4%时，OXY-SME的粒径为（18.69±0.29） nm，PDI为0.181±0.017，包封率为99.87%±1.50%，且乳滴呈类球形，并可将OXY的水中溶解度提高约62倍。通过含水量-电导率拟合曲线和染色法，明确了OXY-SME的乳液类型与含水量的关系。通过测定粒径、PDI和OXY含量等评价了OXY-SME在不同条件下的稳定性，结果表明OXY-SME具有良好的贮存稳定性和稀释稳定性，且能有效延缓光照引起的OXY含量下降。利用SD大鼠腹部皮肤考察了OXY-SME的含水量对OXY皮肤渗透的影响，结果表明在含水量为70%即OXY-SME为O/W型时，OXY的48 h皮肤累积渗透量最高。通过测定体外蘑菇酪氨酸酶及B16-F10细胞内酪氨酸酶活性和黑色素含量评价了OXY-SME的美白活性，结果表明OXY-SME对细胞内酪氨酸酶活性和黑色素生成的抑制作用均要强于OXY水溶液组和阳性对照曲酸（KA）组，OXY-SME具有提高OXY细胞内美白活性的作用。

关键词: 氧化白藜芦醇, 自微乳递送系统, 溶解度, 稳定性, 体外皮肤渗透, 美白活性

Abstract:

A self-microemulsifying drug delivery system （OXY-SME） was developed using Cremophor^® EL and Labrasol^® as composite emulsifiers to efficiently load oxyresveratrol （OXY）, and its formulation characteristics, stability, in vitro skin permeation, and whitening activity were evaluated. Through the pseudo-ternary phase diagram and testing the particle size and polydispersity index （PDI） of the emulsion, the formulation for the preparation of blank self-microemulsion （SME） and the optimal drug loading of OXY were determined. At the optimal drug loading of 4%, the particle size of OXY-SME was （18.69±0.29） nm, with a PDI of 0.181±0.017 and an encapsulation efficiency of 99.87%±1.50%. The emulsion droplets were spherical, and the solubility of OXY in water was increased by approximately 62 times. The relationship between emulsion type and water content of OXY-SME was clarified using water content-conductivity fitting curves and staining methods. The stability of OXY-SME under various conditions was evaluated by measuring particle size, PDI, and OXY content. The results indicate that OXY-SME exhibits good storage stability and dilution stability, and effectively delays the decrease in OXY content caused by light exposure. The effect of water content on OXY skin permeation was investigated using the abdominal skin of SD rats, and the results show that the highest cumulative skin permeation of OXY over 48 hours is observed at a water content of 70%, indicating an oil-in-water （O/W） type emulsion. The whitening activity of OXY-SME was evaluated by measuring the activity of mushroom tyrosinase and intracellular tyrosinase in B16-F10 cells, as well as melanin content. OXY-SME exhibits stronger inhibitory effects on intracellular tyrosinase activity and melanin production compared to OXY aqueous solution and kojic acid （KA） as a positive control, demonstrating that OXY-SME enhances intracellular whitening activity of OXY.

Key words: oxyresveratrol, self-microemulsion delivery system, solubility, stability, in vitro skin penetration, whitening activity

中图分类号:

TQ658

苗开元, 欧阳泽垚, 赵新颖, 杨晓婧, 陈欣妍, 石召华. 氧化白藜芦醇自微乳的制备、表征及美白活性的研究[J]. 日用化学工业（中英文）, 2025, 55(4): 453-463.

Kaiyuan Miao, Zeyao Ouyang, Xinying Zhao, Xiaojing Yang, Xinyan Chen, Zhaohua Shi. Preparation, characterization, and whitening activity research of oxyresveratrol-loaded self-microemulsion[J]. China Surfactant Detergent & Cosmetics, 2025, 55(4): 453-463.

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K_m	m（Labrasol^®）:m（Cremophor^® EL）	m（油相）:m（总乳化剂）	Size/nm	PDI
2:1	1:1	1:9	217.7±4.62	0.276±0.013
2:1	1:1	2:8	17.65±0.49	0.137±0.005
2:1	1:2	1:9	14.69±0.23	0.072±0.002
2:1	1:2	2:8	23.72±0.80	0.214±0.009
2:1	1:3	1:9	15.20±0.56	0.087±0.003
2:1	1:3	2:8	51.28±1.59	0.567±0.136

K_m	m（Labrasol^®）:m（Cremophor^® EL）	m（油相）:m（总乳化剂）	Size/nm	PDI
1:1	1:2	1:9	17.00±0.22	0.137±0.04
2:1	1:2	1:9	14.69±0.16	0.072±0.02
2:1	1:2	2:8	23.72±0.68	0.214±0.09
3:1	1:2	1:9	13.87±0.22	0.123±0.02
3:1	1:2	2:8	17.38±0.56	0.164±0.04
4:1	1:2	1:9	13.28±0.13	0.195±0.08
4:1	1:2	2:8	17.15±0.25	0.159±0.02

OXY投药量/mg	粒径/nm	PDI	包封率/%	载药量/%
5	17.73±0.39	0.140±0.015	99.43±1.43	0.99±0.01
10	17.35±0.19	0.111±0.012	99.61±1.92	1.99±0.03
15	17.64±0.84	0.109±0.021	101.42±2.46	3.04±0.07
20	18.69±0.29	0.181±0.017	99.87±1.50	3.99±0.06
25	26.74±0.70	0.354±0.011	102.44±0.78	5.12±0.03
30	467.06±29.60	0.695±0.021	101.69±1.76	6.10±0.10