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不同相对分子质量透明质酸对还原型谷胱甘肽透皮吸收的影响

Effects of hyaluronic acid with different molecular weight on the transdermal absorption of reduced glutathione

  • 摘要: 研究不同相对分子质量透明质酸(HA)对还原型谷胱甘肽(GSH)在SD大鼠离体皮肤中透皮吸收和储留能力的影响。采用Franz扩散池法考察了不同相对分子质量HA对GSH的体外经皮渗透量及在不同层次皮肤中储留量的影响;利用分子对接AutoDock研究了GSH与HA的相互作用;采用全反射傅里叶红外变换光谱(ATR-FTIR)和H&E切片染色表征HA作用于皮肤后,大鼠角质层中脂质和蛋白的变化及影响。离体透皮实验结果表明,不同相对分子质量的HA对GSH透过皮肤的药量有显著影响,且随着HA的相对分子质量增加,阻碍GSH透过皮肤的作用越强;而在皮肤储留方面,不同相对分子质量的HA均能增加GSH在角质层中的储留量,7 000以下相对分子质量的HA还能显著增加GSH在真皮层中的储留。分子对接结果表明,HA与GSH具有较为强烈的相互作用,可以形成分子间氢键;而ATR-FTIR和HE染色结果则表明,HA可以与皮肤角质层中的脂质与角蛋白发生作用。这种相互作用增加药物的角质层渗透能力,但是作为水溶性的GSH,可能其可以与HA形成分子间氢键的缘故,被网罗在HA水凝胶结构中,从而导致GSH透过完整皮肤的药物量降低;但同时这种相互作用也提供了形成GSH的储库作用,增加了其在皮肤中的储留。通过不同相对分子质量的HA的增加GSH在离体皮肤角质层和真皮层中的储留量的比较,结果显示,低相对分子质量的HA储留能力最好。

     

    Abstract: This paper aimed at studying the effects of hyaluronic acid (HA) with different molecular weights on the transdermal absorption and retention of reduced glutathione (GSH) in the isolated skin of SD rats. Franz diffusion cell method was used to investigate the effects with different molecular weights HA on the in vitro transdermal penetration of GSH and the storage in different layers of the skin. AutoDock molecular docking was used to study the interaction between GSH and HA. Attenuated total reflection Fourier transformed infrared spectroscopy (ATR-FTIR) and H&E section staining were used to characterize the changes and effects of lipids and proteins in the rat stratum corneum after HA acts on the skin. The results of in vitro transdermal experiments showed that HA with different molecular weights had a significant impact on the amount of GSH passing through the skin, that as the molecular weight of HA increased, the effect of preventing GSH from passing through the skin became stronger, that in terms of skin storage, HA with different molecular weights could increase the storage of GSH in the stratum corneum, and that HA with a molecular weight below 7K could also significantly increase the storage of GSH in the dermis. The molecular docking results showed that HA and GSH had a relatively strong interaction, which could form intermolecular hydrogen bonds; and the results of ATR-FTIR and H&E staining showed that HA could interact with lipids and keratins in the stratum corneum of the skin. Such interaction can increase the permeability of the stratum corneum of the drug, however, as a water-soluble GSH, it may be involved in the formation of intermolecular hydrogen bonds with HA. In the structure of HA hydrogel, the amount of GSH drug passing through the intact skin is reduced; but at the same time, this interaction also provides a reservoir for the formation of GSH, thus increasing its storage in the skin. Through comparison of the storage capacity of GSH in the stratum corneum and dermis of the isolated skin due to the increase of HA with different molecular weights, it has been found that the storage capacity of HA with low relative molecular weight is the best.

     

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