评估皮肤渗透增强剂 Putocrin®的安全性和有效性。

Evaluation of the safety and efficacy of skin penetration enhancer Putocrin®.

机构信息

Guangzhou Luanying Cosmetics Co., Ltd, Guangzhou, China.

Centre for Biotech Big Data Research & Development, Research Institute of Tsinghua, Pearl River Delta, China.

出版信息

J Cosmet Dermatol. 2024 Oct;23(10):3272-3280. doi: 10.1111/jocd.16409. Epub 2024 Jun 12.

DOI:10.1111/jocd.16409

PMID:38867384

Abstract

BACKGROUND

Substances that can efficiently enhance skin penetration while exerting no adverse effect are useful for drug and cosmetics formulation.

OBJECTIVE

To investigate the safety and enhance skin penetration efficacy of Putocrin®, a combination containing 2% isosorbide dimethyl ether, 1% pentanediol, and 0.5% inositol.

METHODS

An in vitro keratinocyte cell assay using 3-(4,5-dimethylthiazolyl-2)-2,5 diphenyltetrazolium bromide (MTT), and an in vitro EpiKutis® skin study adopted hematoxylin and eosin staining, immunostaining, and liquid chromatography-mass spectrometry (LC-MS) analysis were carried out to investigate the safety of Putocrin®. A pigskin-Franz cell system experiment applied high-performance liquid chromatography (HPLC) to compare the skin penetration efficiency of fluorescein isothiocyanate (Fitc)-labeled tranexamic acid with or without the assistance of Putocrin®. The safety and efficacy of Putocrin® was further evaluated on zebrafish embryos.

RESULTS

The MTT assay showed that Putocrin® at concentration ≤2.5% did not significantly affect cell viability. The in vitro EpiKutis® skin study revealed that 2.5% Putocrin® did not affect skin morphology, filaggrin content, ceramide/protein, or fatty acid/protein ratios, but significantly increased loricrin content by 86.00% (p < 0.001). The pigskin-Franz cell penetration experiment demonstrated that Fitc-labeled tranexamic acid could barely penetrate the skin (with penetration rate of 1.121%), while Putocrin® significantly enhanced the penetration rate up to 83.983%, which was close to unlabeled tranexamic acid (90.013%). The zebrafish embryo study showed that 2.5% Putocrin® did not exert observable toxicity and obviously assisted the skin penetration of Fitc-labeled tranexamic acid into fish embryos. These results indicate the strong enhancing skin penetration potency of Putocrin®.

CONCLUSION

This study demonstrated the safety as well as the strong enhancing skin penetration potency of Putocrin® for cosmetics formulation use.

摘要

背景

能够有效促进皮肤渗透而无不良反应的物质，对于药物和化妆品制剂非常有用。

目的

研究含有 2%异山梨醇二甲醚、1%戊二醇和 0.5%肌醇的 Putocrin®的安全性和增强皮肤渗透效果。

方法

采用 3-(4,5-二甲基噻唑基-2)-2,5-二苯基四氮唑溴盐（MTT）进行体外角质形成细胞试验，采用苏木精和伊红染色、免疫染色和液相色谱-质谱（LC-MS）分析进行体外 EpiKutis®皮肤研究，以研究 Putocrin®的安全性。应用高效液相色谱（HPLC）比较在或不在 Putocrin®辅助下，荧光素异硫氰酸酯（Fitc）标记氨甲环酸的皮肤渗透效率，在猪皮 Franz 细胞系统实验中进行。进一步在斑马鱼胚胎上评价 Putocrin®的安全性和功效。

结果

MTT 试验表明，浓度≤2.5%的 Putocrin®对细胞活力无显著影响。体外 EpiKutis®皮肤研究显示，2.5%Putocrin®不影响皮肤形态、丝聚蛋白含量、神经酰胺/蛋白和脂肪酸/蛋白比值，但可显著增加 86.00%（p<0.001）的角蛋白含量。猪皮 Franz 细胞渗透实验表明，Fitc 标记氨甲环酸几乎不能穿透皮肤（渗透速率为 1.121%），而 Putocrin®可显著将渗透速率提高至 83.983%，接近未标记氨甲环酸（90.013%）。斑马鱼胚胎研究显示，浓度为 2.5%的 Putocrin®无明显毒性，并能明显促进 Fitc 标记氨甲环酸进入鱼胚胎的皮肤渗透。这些结果表明 Putocrin®具有很强的增强皮肤渗透能力。