载姜黄素自乳化药物传递系统（SEDDS）的制剂学与特性研究及其在皮肤和黏膜利什曼病中的局部应用。
Formulation and Characterization of a Self-Emulsifying Drug Delivery System (SEDDS) of Curcumin for the Topical Application in Cutaneous and Mucocutaneous Leishmaniasis.
机构信息
Department of Biotechnology, Quaid-i-Azam University, Islamabad, Pakistan.
Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan.
出版信息
Curr Top Med Chem. 2018;18(18):1603-1609. doi: 10.2174/1568026618666181025104818.
BACKGROUND
Leishmaniasis, which is classified by the World Health Organization (WHO) as one of the Neglected Tropical Diseases (NTDs) faces several challenges in terms of successful chemotherapy and novel drug developments.
OBJECTIVE
The aim of the present study was to develop a Self-Emulsifying Drug Delivery System (SEDDS) for the hydrophobic polyphenol pigment curcumin to enable it for its potential use in cutaneous and mucocutaneous leishmaniasis.
METHODS
Two Curcumin-loaded formulations SNEDD-A and B, were developed. Both were characterized by the droplet size, PDI and zeta potential and evaluated for the cytotoxicity on Caco-2 cell lines and through hemolysis test on red blood cells. The spreading potential of the formulations was checked over buccal mucosa and damaged skin model. Antileishmanial activities were performed against promastigote, axenic amastigote and macrophage harbored amastigotes of Leishmania tropica parasite.
RESULTS
SNEDDS-A and B had minor differences in physical characteristics. In the toxicological assay, the viability of the Caco-2 cells was 87.5 % for SNEDDS-A and 88.9% for SNEDDS-B while both caused 1-2% hemolysis. Both had remarkable spreading potential, covering 8cm2 of buccal mucosa and damaged the skin for less than 45 minutes. The Antileishmanial activities of the SNEDDS-A in terms of IC50 were 0.13 µg/ml and 0.25 µg/ml against promastigote and amastigote, respectively while IC50 values of SNEDDS-B were 0.18 µg/ml and 0.27 µg/ml against promastigote and amastigote, respectively. Both the formulations killed 100% of the macrophage harbored Leishmania tropica parasites at a concentration of 4.4 µg/ml.
CONCLUSION
Our results demonstrate that both the SEDDS formulations of curcumin have the potential to provide a promising tool for curcumin for its use through topical routes in the treatment of cutaneous and mucocutaneous leishmaniasis.
背景
利什曼病被世界卫生组织（WHO）列为被忽视的热带病（NTDs）之一，在成功化疗和新药物开发方面面临诸多挑战。
目的
本研究旨在开发一种自乳化药物传递系统（SEDDS），用于疏水性多酚色素姜黄素，使其有可能用于皮肤和粘膜利什曼病的治疗。
方法
研制了两种载有姜黄素的制剂 SNEDD-A 和 B，通过粒径、PDI 和 Zeta 电位对其进行了表征，并对 Caco-2 细胞系的细胞毒性进行了评价，还对红细胞的溶血试验进行了评价。对制剂在口腔粘膜和损伤皮肤模型上的铺展潜力进行了检查。对利什曼原虫的前鞭毛体、无鞭毛体和巨噬细胞内的无鞭毛体进行了抗利什曼原虫活性试验。
结果
SNEDDS-A 和 B 在物理特性上有微小的差异。在毒理学试验中，SNEDDS-A 的 Caco-2 细胞活力为 87.5%，SNEDDS-B 的活力为 88.9%，而两者的溶血率均为 1-2%。两种制剂都有显著的铺展潜力，在 45 分钟内覆盖 8cm2 的口腔粘膜和损伤皮肤。SNEDDS-A 的抗利什曼原虫活性（以 IC50 表示）对前鞭毛体和无鞭毛体分别为 0.13µg/ml 和 0.25µg/ml，而 SNEDDS-B 的 IC50 值分别为 0.18µg/ml 和 0.27µg/ml。两种制剂在 4.4µg/ml 的浓度下均能杀死 100%的含有利什曼原虫的巨噬细胞。
结论
我们的结果表明，姜黄素的两种 SEDDS 制剂都有可能为姜黄素通过局部途径治疗皮肤和粘膜利什曼病提供一种有前途的工具。
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