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熊果苷水凝胶作为皮肤美白剂制剂的绿色制备、表征、抗黑色素生成作用评价及安全性概况。

Green preparation, characterization, evaluation of anti-melanogenesis effect and / safety profile of kojic acid hydrogel as skin lightener formulation.

机构信息

Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.

Pharmaceutical Sciences Research Centre, Heamoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran.

出版信息

J Biomater Sci Polym Ed. 2022 Dec;33(17):2270-2291. doi: 10.1080/09205063.2022.2103624. Epub 2022 Jul 26.

Abstract

The local treatment of kojic acid (KA) as a tyrosinase inhibitor results in inadequate skin absorption and a number of side effects. The current study aims to maximize KA skin delivery. To produce KA-hydrogel, 1% KA was injected into a Chitosan/alginate hydrogel. The impacts of biopolymer proportion on the KA-hydrogel preparations were investigated. Swelling analysis, weight loss analysis, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), UV absorption spectroscopy, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy were used to evaluate the KA-hydrogel. The swelling percentages of KA-hydrogel increased significantly after 4 h. After two weeks, up to 60% of the primary mass of the KA- hydrogel has been removed. By alternation in biopolymer proportion, the drug release profile of KA-hydrogel demonstrated a sustained pattern. According to the skin absorption experiment, KA-hydrogel had higher skin deposition (25.630 ± 3.350%) than KA-plain gel (5.170 ± 0.340%). Moreover, an cytotoxicity analysis for the modified KA-hydrogel preparations revealed no cytotoxic effects on HFF cell line (90%). Moreover, KA hydrogel had inhibitory effect on melanin synthesis and are comparable with KA. Furthermore, KA-hydrogel had higher inhibitory effect on L-dopa auto oxidation (94.84 ± 2.41%) in comparison KA solution (73.95 ± 3.28%). Also, the dermal irritation study on Wistar rat revealed that the hydrogel constituent used did not irritate the skin. These results revealed that the KA-hydrogel might be employed as KA local administration, thus opening up new prospects for the therapies of hyperpigmentation problems.

摘要

曲酸(KA)作为一种酪氨酸酶抑制剂的局部治疗导致皮肤吸收不足和许多副作用。本研究旨在最大限度地提高 KA 的皮肤传递。为了生产 KA-水凝胶,将 1%的 KA 注入壳聚糖/海藻酸钠水凝胶中。研究了生物聚合物比例对 KA-水凝胶制剂的影响。通过溶胀分析、失重分析、差示扫描量热法(DSC)、扫描电子显微镜(SEM)、紫外吸收光谱、衰减全反射傅里叶变换红外(ATR-FTIR)光谱对 KA-水凝胶进行了评价。KA-水凝胶的溶胀百分比在 4 小时后显著增加。两周后,KA-水凝胶的初始质量中有高达 60%被去除。通过改变生物聚合物的比例,KA-水凝胶的药物释放曲线呈现出持续的模式。根据皮肤吸收实验,KA-水凝胶的皮肤沉积量(25.630±3.350%)高于 KA-普通凝胶(5.170±0.340%)。此外,对改良 KA-水凝胶制剂的细胞毒性分析显示,对 HFF 细胞系无细胞毒性(90%)。此外,KA 水凝胶对黑色素合成具有抑制作用,与 KA 相当。此外,KA-水凝胶对 L-多巴自动氧化的抑制作用(94.84±2.41%)高于 KA 溶液(73.95±3.28%)。此外,对 Wistar 大鼠的皮肤刺激性研究表明,水凝胶成分不会刺激皮肤。这些结果表明,KA-水凝胶可作为 KA 的局部给药,为色素沉着问题的治疗开辟了新的前景。

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