State-Province Joint Engineering Laboratory of Marine Bioproducts and Technology, Department of Marine Biological Science & Technology, College of Ocean & Earth Science, Xiamen University, Xiamen, 361102, China.
Department of Cardiology, Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, China.
Pharm Res. 2020 May 20;37(6):100. doi: 10.1007/s11095-020-02800-4.
We investigated the potential correlations between skin barrier integrity and hydrophilic drugs distribution in skin in the presence of different types of penetration enhancers (PEs) and their combinations.
We measured skin conductivity to evaluate skin barrier integrity before and after the topical application of different chemical PEs, physical PE, peptide PE and their combinations in vitro. We also investigated their effect on the skin distribution profiles of two hydrophilic model drugs, Fluorescein sodium (376 Da) and Fluorescein isothiocyanate-dextrans 10 (10 KDa).
The physical PE significantly increased the skin conductivity compared to all other PEs, while the peptide PE had no effect on it. The drug deposition in different skin layers was not only dependent on PE applied but also its own molecular weight. We further found two excellent correlations: one (R = 0.9388) between skin barrier integrity and total skin absorption of FNa and another one(R = 0.9212) between skin barrier integrity and the deposition of FNa in dermis and receptor in presence of chemical or physical PEs and their combinations.
The total skin absorption or the deposition in dermis and receptor of small hydrophilic drug in the presence of chemical and physical PEs and their combinations show a good correlation with skin barrier integrity. However, such correlations hold true neither for large hydrophilic drug nor for peptide PE. All good relationships found in this work will allow screening suitable PEs or combinations by measuring the skin conductivity induced by corresponding PEs. Graphical Abstract The total skin absorption of small hydrophilic drug shows a good correlation with skin barrier integrity in the presence of chemical and physical penetration enhancers and their combinations. However, such a correlation hold true neither for large hydrophilic drug nor for peptide penetration enhancer.
本研究旨在探讨不同类型（化学和物理）经皮渗透促进剂（PEs）及其组合对皮肤屏障完整性和皮肤内亲水性药物分布的潜在相关性。
我们通过测量皮肤电导率来评估不同化学 PEs、物理 PE、肽 PE 及其组合在体外经皮应用前后的皮肤屏障完整性。同时，我们还研究了它们对两种亲水性模型药物（荧光素钠（376 Da）和荧光素异硫氰酸酯-葡聚糖 10（10 kDa））在皮肤中分布的影响。
与其他所有 PEs 相比，物理 PE 显著增加了皮肤电导率，而肽 PE 对其没有影响。不同皮肤层中的药物沉积不仅依赖于应用的 PE，还与其自身分子量有关。我们进一步发现了两个很好的相关性：一个（R=0.9388）是皮肤屏障完整性与 FNa 的总皮肤吸收之间的相关性，另一个（R=0.9212）是皮肤屏障完整性与 FNa 在真皮和受体中的沉积之间的相关性，在化学或物理 PEs 及其组合存在的情况下。
在化学和物理 PEs 及其组合存在的情况下，小分子亲水性药物的总皮肤吸收或在真皮和受体中的沉积与皮肤屏障完整性之间存在良好的相关性。然而，对于大的亲水性药物和肽 PE，这种相关性并不成立。本工作中发现的所有良好关系都可以通过测量相应 PEs 引起的皮肤电导率来筛选合适的 PEs 或组合。
