Investigating the influence of drug aggregation on the percutaneous penetration rate of tetracaine when applying low doses of the agent topically to the skin
Investigating the influence of drug aggregation on the percutaneous penetration rate of tetracaine when applying low doses of the agent topically to the skin
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DOI：
10.1016/j.ijpharm.2016.02.007
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发表时间：
2016-04-11
影响因子：
5.8
通讯作者：
Jones, S. A.
中科院分区：
文献类型：
--
作者：
Cai, X. J.;Patel, T.;Jones, S. A.
当将低剂量的药物应用于皮肤表面时，了解治疗剂的分子聚集特别重要。本研究的目的是了解药物的浓度如何影响其分子聚集和局部应用后的经皮渗透。模型药物丁卡因显示在μ M（荧光光谱）至mM（光散射分析）浓度范围内形成一系列不同的聚集体。聚集体形成过程对药物溶解于其中的载体的pH敏感（pH 4，临界聚集浓度（CAC）-11 μ M; pH 8，CAC - 7 μ M），并且它似乎对药物的经皮渗透具有影响。在pH 4时，随着供体溶液中药物浓度的增加，丁卡因的皮肤渗透系数（K-p）减小（13.7 +/- 4.3 x 10（3）cm/h至0.06 +/- 0.02 x 10（3）cm/h），而在pH 8时，增加了K-p（29.9 +/- 9.9 x 10（3）cm/h至75.1 +/- 41.7 x 10（3）cm/h）。这些数据趋势在硅胶膜中重现，这支持了以下观点：在pH 4下形成的极性更强的聚集体降低了可通过皮肤的物质的比例，而在pH 8下形成的疏水性更强的聚集体增加了膜扩散物质。(C)2016爱思唯尔B. V.保留所有权利。
Understanding the molecular aggregation of therapeutic agents is particularly important when applying low doses of a drug to the surface of the skin. The aim of this study was to understand how the concentration of a drug influenced its molecular aggregation and its subsequent percutaneous penetration after topical application. A model drug tetracaine was shown to form a series of different aggregates across the mu M (fluorescence spectroscopy) to mM (light scattering analysis) concentration range. The aggregate formation process was sensitive to the pH of the vehicle in which the drug was dissolved (pH 4, critical aggregation concentration (CAC) - 11 mu M; pH 8, CAC - 7 mu M) and it appeared to have an impact upon the drug's percutaneous penetration. At pH 4, increasing the concentration of the drug in the donor solution decreased the skin permeability coefficient (K-p) of tetracaine (13.7 +/- 4.3 x 10 (3) cm/h to 0.06 +/- 0.02 x 10 (3) cm/h), whilst at pH 8, it increased the K-p (29.9 +/- 9.9 x 10 (3) cm/h to 75.1 +/- 41.7 x 10 (3) cm/h). These data trends were reproduced in a silicone membrane and this supported the notion that the more polar aggregates formed at pH 4 acted to decrease the proportion of species available to pass through the skin, whilst the more hydrophobic aggregates formed in pH 8 increased the membrane diffusing species. (C) 2016 Elsevier B.V. All rights reserved.