Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences & Research Centre, Amrita Vishwa Vidyapeetham, Cochin 682041, India.
Nanoscale. 2012 Jan 7;4(1):239-50. doi: 10.1039/c1nr11271f. Epub 2011 Nov 14.
In this study, curcumin loaded chitin nanogels (CCNGs) were developed using biocompatible and biodegradable chitin with an anticancer curcumin drug. Chitin, as well as curcumin, is insoluble in water. However, the developed CCNGs form a very good and stable dispersion in water. The CCNGs were analyzed by DLS, SEM and FTIR and showed spherical particles in a size range of 70-80 nm. The CCNGs showed higher release at acidic pH compared to neutral pH. The cytotoxicity of the nanogels were analyzed on human dermal fibroblast cells (HDF) and A375 (human melanoma) cell lines and the results show that CCNGs have specific toxicity on melanoma in a concentration range of 0.1-1.0 mg mL(-1), but less toxicity towards HDF cells. The confocal analysis confirmed the uptake of CCNGs by A375. The apoptotic effect of CCNGs was analyzed by a flow-cytometric assay and the results indicate that CCNGs at the higher concentration of the cytotoxic range showed comparable apoptosis as the control curcumin, in which there was negligible apoptosis induced by the control chitin nanogels. The CCNGs showed a 4-fold increase in steady state transdermal flux of curcumin as compared to that of control curcumin solution. The histopathology studies of the porcine skin samples treated with the prepared materials showed loosening of the horny layer of the epidermis, facilitating penetration with no observed signs of inflammation. These results suggest that the formulated CCNGs offer specific advantage for the treatment of melanoma, the most common and serious type of skin cancer, by effective transdermal penetration.
在这项研究中，使用生物相容性和可生物降解的壳聚糖开发了负载姜黄素的壳聚糖纳米凝胶（CCNGs），并结合了一种抗癌姜黄素药物。壳聚糖和姜黄素都不溶于水。然而，所开发的 CCNGs 在水中形成了非常好且稳定的分散体。通过 DLS、SEM 和 FTIR 对 CCNGs 进行了分析，结果表明其为粒径在 70-80nm 范围内的球形颗粒。与中性 pH 相比，CCNGs 在酸性 pH 下具有更高的释放率。纳米凝胶的细胞毒性在人真皮成纤维细胞（HDF）和 A375（人黑素瘤）细胞系上进行了分析，结果表明 CCNGs 在 0.1-1.0mg/mL 的浓度范围内对黑素瘤具有特异性毒性，但对 HDF 细胞的毒性较小。共聚焦分析证实了 A375 对 CCNGs 的摄取。通过流式细胞术分析了 CCNGs 的凋亡作用，结果表明，在细胞毒性范围内较高浓度的 CCNGs 表现出与对照姜黄素相当的凋亡作用，而对照壳聚糖纳米凝胶几乎没有诱导凋亡。与对照姜黄素溶液相比，CCNGs 使姜黄素的稳态透皮通量增加了 4 倍。用制备的材料处理的猪皮样品的组织病理学研究表明，表皮角质层松动，有利于渗透，且未观察到炎症迹象。这些结果表明，所制备的 CCNGs 通过有效的透皮渗透为治疗最常见和最严重的皮肤癌——黑素瘤提供了特定的优势。
