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通过微流控技术优化穿心莲内酯纳米乳剂的生产参数及其对皮肤癌细胞和紫外线B辐射暴露皮肤的生物活性评估

Optimization of Production Parameters for Andrographolide-Loaded Nanoemulsion Preparation by Microfluidization and Evaluations of Its Bioactivities in Skin Cancer Cells and UVB Radiation-Exposed Skin.

作者信息

Asasutjarit Rathapon, Sooksai Nawarat, Fristiohady Adryan, Lairungruang Kriyapa, Ng Shiow-Fern, Fuongfuchat Asira

机构信息

Thammasat University Research Unit in Drug, Health Product Development and Application (DHP-DA), Department of Pharmaceutical Sciences, Faculty of Pharmacy, Thammasat University, Pathum Thani 12120, Thailand.

Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Halu Oleo, Kendari 93132, Indonesia.

出版信息

Pharmaceutics. 2021 Aug 18;13(8):1290. doi: 10.3390/pharmaceutics13081290.

DOI:10.3390/pharmaceutics13081290
PMID:34452250
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8399116/
Abstract

Andrographolide (AG) is an active compound isolated from (Family Acanthaceae). Although it possesses beneficial bioactivities to the skin, there is insufficient information of its applications for treatment of skin disorders due to low water solubility leading to complications in product development. To overcome the problem, an AG-loaded nanoemulsion (AG-NE) was formulated and prepared using a microfluidization technique. This study aimed to investigate the effect of pressure and the number of homogenization cycles (factors) on droplet size, polydispersity index and zeta potential of AG-NE (responses) and to determine the effect of AG-NE on skin cancer cells and UVB irradiation-induced skin disorders in rats. Relationships between factors versus responses obtained from the face-centered central composite design were described by quadratic models. The optimum value of parameters for the production of optimized AG-NE (Op-AG-NE) were 20,000 psi of pressure and 5 homogenization cycles. Op-AG-NE showed promising cytotoxicity effects on the human malignant melanoma- (A375 cells) and non-melanoma cells (A-431 cells) via apoptosis induction with a high selectivity index and also inhibited intracellular tyrosinase activity in the A375 cells. Op-AG-NE could reduce melanin index and healed UVB irradiation exposed skin. Op-AG-NE thus had potential for treatment of skin cancers and skin disorders from exposure to UVB radiation.

摘要

穿心莲内酯(AG)是从爵床科植物中分离出的一种活性化合物。尽管它对皮肤具有有益的生物活性,但由于其低水溶性导致产品开发出现并发症,关于其在治疗皮肤疾病方面的应用信息不足。为克服这一问题,采用微流化技术制备了载穿心莲内酯纳米乳剂(AG-NE)。本研究旨在探讨压力和匀化循环次数(因素)对AG-NE的粒径、多分散指数和zeta电位(响应)的影响,并确定AG-NE对大鼠皮肤癌细胞和紫外线B(UVB)辐射诱导的皮肤疾病的作用。通过二次模型描述了从面心中央复合设计获得的因素与响应之间的关系。制备优化的AG-NE(Op-AG-NE)的最佳参数值为压力20000 psi和5次匀化循环。Op-AG-NE通过诱导凋亡对人恶性黑色素瘤细胞(A375细胞)和非黑色素瘤细胞(A-431细胞)显示出有前景的细胞毒性作用,且具有高选择性指数,还抑制A375细胞内酪氨酸酶活性。Op-AG-NE可降低黑色素指数并治愈UVB辐射暴露的皮肤。因此,Op-AG-NE在治疗皮肤癌和UVB辐射引起的皮肤疾病方面具有潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d03/8399116/36051d8f8675/pharmaceutics-13-01290-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d03/8399116/94b216b2de9d/pharmaceutics-13-01290-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d03/8399116/5c2effd1f226/pharmaceutics-13-01290-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d03/8399116/36051d8f8675/pharmaceutics-13-01290-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d03/8399116/c652dfd3d690/pharmaceutics-13-01290-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d03/8399116/1c55bfab0b25/pharmaceutics-13-01290-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d03/8399116/7d2c72ba8426/pharmaceutics-13-01290-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d03/8399116/0bc4c80c6c7e/pharmaceutics-13-01290-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d03/8399116/94b216b2de9d/pharmaceutics-13-01290-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d03/8399116/36051d8f8675/pharmaceutics-13-01290-g008.jpg

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