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用于局部给药的姜黄素和姜黄酮负载固体脂质纳米粒的研制:采用3D组织模型进行优化、表征及皮肤刺激性评估

Development of Curcumin and Turmerone Loaded Solid Lipid Nanoparticle for Topical Delivery: Optimization, Characterization and Skin Irritation Evaluation with 3D Tissue Model.

作者信息

Aydin Beyza Sümeyye, Sagiroglu Ali Asram, Ozturk Civelek Dilek, Gokce Mustafa, Bahadori Fatemeh

机构信息

Bezmialem Vakif University, Health Sciences Institute, Department of Biotechnology, Istanbul, 34093, Turkey.

Istanbul University-Cerrahpasa, Faculty of Pharmacy, Department of Pharmaceutical Technology, Istanbul, 34500, Turkey.

出版信息

Int J Nanomedicine. 2024 Feb 26;19:1951-1966. doi: 10.2147/IJN.S453347. eCollection 2024.

Abstract

BACKGROUND

Curcuma longa L., commonly known as turmeric, is renowned for its therapeutic benefits attributed to bioactive compounds, namely curcumin (Cur) and aromatic turmerone (Tur), present in its rhizome. These compounds exhibit diverse therapeutic properties, including anti-inflammatory, antioxidant, and anti-tumor effects. However, the topical application of these compounds has a significant potential for inducing skin irritation. This study focuses on formulating solid lipid nanoparticle (SLN) carriers encapsulating both Cur and Tur for reduced irritation and enhanced stability.

METHODS

SLN formulations were prepared by a method using homogenization followed by ultrasonication procedures and optimized by applying response surface methodology (RSM).

RESULTS

The optimized SLN formulation demonstrated entrapment efficiencies, with 77.21 ± 4.28% for Cur and 75.12 ± 2.51% for Tur. A size distribution of 292.11 ± 9.43 nm was obtained, which was confirmed to be a spherical and uniform shape via environmental scanning electron microscopy (ESEM) images. The in vitro release study indicated cumulative releases of 71.32 ± 3.73% for Cur and 67.23 ± 1.64% for Tur after 24 hours under sink conditions. Physical stability tests confirmed the stability of formulation, allowing storage at 4°C for a minimum of 60 days. Notably, in vitro skin irritation studies, utilizing the reconstructed human epidermal model (EPI-200-SIT), revealed a significant reduction in irritation with the SLN containing Cur and Tur compared to nonencapsulated Cur and Tur.

CONCLUSION

These findings collectively endorse the optimized SLN formulation as a favorable delivery system for Cur and Tur in diverse topical uses, offering enhanced stability, controlled release and reduced irritation.

摘要

背景

姜黄(Curcuma longa L.),俗称姜黄根粉,因其根茎中存在的生物活性化合物,即姜黄素(Cur)和芳香姜黄酮(Tur)而具有治疗功效而闻名。这些化合物具有多种治疗特性,包括抗炎、抗氧化和抗肿瘤作用。然而,这些化合物的局部应用有很大的潜在皮肤刺激性。本研究重点在于制备同时包封Cur和Tur的固体脂质纳米粒(SLN)载体,以减少刺激性并提高稳定性。

方法

采用均化后超声处理的方法制备SLN制剂,并应用响应面法(RSM)进行优化。

结果

优化后的SLN制剂显示出包封率,Cur为77.21±4.28%,Tur为75.12±2.51%。获得的粒径分布为292.11±9.43nm,通过环境扫描电子显微镜(ESEM)图像证实其为球形且均匀。体外释放研究表明,在漏槽条件下24小时后,Cur的累积释放率为71.32±3.73%,Tur为67.23±1.64%。物理稳定性测试证实了制剂的稳定性,允许在4°C下储存至少60天。值得注意的是,利用重建的人表皮模型(EPI-200-SIT)进行的体外皮肤刺激性研究表明,与未包封的Cur和Tur相比,含有Cur和Tur的SLN的刺激性显著降低。

结论

这些发现共同支持优化后的SLN制剂作为Cur和Tur在各种局部应用中的良好递送系统,具有增强的稳定性、控释性和降低的刺激性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/898d/10907133/b58104125818/IJN-19-1951-g0001.jpg

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