Peng Li-Hua, Xu Shen-Yao, Shan Ying-Hui, Wei Wei, Liu Shuai, Zhang Chen-Zhen, Wu Jia-He, Liang Wen-Quan, Gao Jian-Qing
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China.
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China ; Novel Transdermal Research Center of Jiangsu Province, Changzhou, People's Republic of China.
Int J Nanomedicine. 2014 Apr 16;9:1897-908. doi: 10.2147/IJN.S59290. eCollection 2014.
Melanin is the one of most important pigments for skin color in mammals. Excessive biosynthesis of melanin induces various pigment disorders. Much effort has been made to develop regulators to minimize skin pigmentation abnormalities. However, only a few of them are used, primarily because of safety concerns and low efficiency. In this study, we aimed to construct a novel nanosphere-gel for sequential delivery of salidroside and paeonol, to investigate the synergistic effects of these drugs in anti-melanogenesis, and to decrease their potential for toxicity in high dosage. Nanospheres were prepared and characterized for their particle size, polydispersity index, zeta potential, and morphological properties. The optimized nanospheres were incorporated in carbomer hydrogel with both paeonol and salidroside entrapped to form a dual drug-releasing nanosphere-gel. With this nanosphere-gel, rapid release of salidroside from the hydrogel followed by sustained release of paeonol from the nanosphere was achieved. Using a classical model of the melanogenesis response to ultraviolet exposure, it was shown that the anti-melanogenesis effects of the dual drug-releasing system, in which the doses of the individual drugs were decreased by half, was obviously enhanced when compared with the effects of the single drug preparations. Mechanistically, the burst release of salidroside from the hydrogel may enable prompt suppression of melanocyte proliferation on exposure to ultraviolet B radiation, while the paeonol released in a sustained manner can provide continuous inhibition of tyrosinase activity in melanocytes. Combined delivery of salidroside and paeonol was demonstrated to be a promising strategy for enhancing the therapeutic efficacy of these agents in anti-melanogenesis and reducing their toxicity, so may have great potential in nanomedicine.
黑色素是哺乳动物皮肤颜色最重要的色素之一。黑色素的过度生物合成会引发各种色素紊乱。人们已付出诸多努力来开发调节剂，以尽量减少皮肤色素沉着异常。然而，其中只有少数几种被使用，主要是出于安全性担忧和效率低下的原因。在本研究中，我们旨在构建一种新型纳米球凝胶，用于红景天苷和丹皮酚的序贯递送，研究这些药物在抗黑色素生成中的协同作用，并降低其高剂量时的潜在毒性。制备了纳米球并对其粒径、多分散指数、zeta电位和形态特性进行了表征。将优化后的纳米球与丹皮酚和红景天苷一起包封在卡波姆水凝胶中，形成一种双药释放纳米球凝胶。通过这种纳米球凝胶，实现了红景天苷从水凝胶中的快速释放，随后丹皮酚从纳米球中的持续释放。使用紫外线照射后黑色素生成反应的经典模型表明，与单药制剂的效果相比，双药释放系统（其中各药物剂量减半）的抗黑色素生成效果明显增强。从机制上讲，红景天苷从水凝胶中的突发释放可能能够在暴露于紫外线B辐射时迅速抑制黑素细胞增殖，而持续释放的丹皮酚可以持续抑制黑素细胞中的酪氨酸酶活性。红景天苷和丹皮酚的联合递送被证明是一种有前景的策略，可增强这些药物在抗黑色素生成中的治疗效果并降低其毒性，因此在纳米医学中可能具有巨大潜力。
