The Role of the Conformational Profile of Polysaccharides on Skin Penetration: The Case of Hyaluronan and Its Sulfates
The Role of the Conformational Profile of Polysaccharides on Skin Penetration: The Case of Hyaluronan and Its Sulfates
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DOI：
10.1002/cbdv.201300130
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发表时间：
2014-04-01
影响因子：
2.9
通讯作者：
Minghetti, Paola
中科院分区：
文献类型：
--
作者：
Cilurzo, Francesco;Vistoli, Giulio;Minghetti, Paola
文献数据表明生物大分子渗透人体皮肤的能力，即使这样的经皮渗透似乎是由物理化学参数，这是显着不同的那些统治的小分子的皮肤渗透相比。基于此，本研究旨在探讨透明质酸及其硫酸盐在人体表皮中的体外扩散特性。然后测试了低分子量和中分子量的透明质酸和相应的两个硫酸化度的衍生物。体外研究证明，硫酸化聚合物比相应的透明质酸渗透更好，尽管它们的极性大得多，而当增加聚合物的分子量时，观察到的渗透显著降低，而不管硫酸化程度如何。使用荧光标记的多糖，还证明透明质酸对角质细胞具有很大的亲和力，并且可能主要通过跨细胞途径穿过角质层。分子动力学研究揭示了如何观察到的渗透调查多糖可以合理化，通过监测其构象配置文件，因为渗透被发现是直接相关的，他们的能力，承担扩展和灵活的构象。
The literature data suggest the capacity of biomacromolecules to permeate the human skin, even though such a transdermal permeation appears to be governed by physicochemical parameters which are significantly different compared to those ruling the skin permeation of small molecules. On these grounds, the present study was undertaken to investigate the in vitro diffusion properties through the human epidermis of hyaluronic acid and their sulfates. Low- and medium-molecular-weight hyaluronic acids and the corresponding derivatives at two degrees of sulfation were then tested. In vitro studies evidenced that the sulfated polymers permeate better than the corresponding hyaluronic acid, despite their vastly greater polarity, while the observed permeation markedly decreases when increasing the polymer's molecular weight regardless of the sulfation degree. Using a fluorescent-labeled polysaccharide, it was also evidenced that hyaluronans have a great affinity for corneocytes and likely cross the stratum corneum mainly through a transcellular route. The molecular-dynamics study revealed how the observed permeations for the investigated polysaccharides can be rationalized by monitoring their conformational profiles, since the permeation was found to be directly related to their capacity to assume extended and flexible conformations.