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Correlations Between Skin Barrier Integrity and Delivery of Hydrophilic Molecules in the Presence of Penetration Enhancers

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Abstract

Purpose

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.

Methods

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).

Results

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 (R2 = 0.9388) between skin barrier integrity and total skin absorption of FNa and another one(R2 = 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.

Conclusions

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.

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.

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Acknowledgements and Disclosures

This work was supported in part by Science and Technology Planning Project of Fujian Province, China (Grant No. 2017Y4015), Marine Economic Development Subsidy Project of Fujian Province, China(Grant No. FJHJF-L-2019-03), Medical Elite Cultivation Program of Fujian Province, China (Grant No. 2015-ZQN-ZD-24). M.C. designed the experiments. X.L., Z.W. and H.O. performed the experiments. X.L. and M.C. wrote the article with the help of S.M.. All the authors were involved in the analyses and interpretation of data. We thank Yuhao Lu for assistance with spicule purification, Saiman Zhang for assistance with the preparation of porcine skin. There are no conflicts to declare.

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Author notes

  1. XueKe Lin and ZhenHua Wang contributed equally to this work.

Authors and Affiliations

  1. 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

    XueKe Lin, HuiLong Ou & Ming Chen

  2. Department of Cardiology, Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, China

    ZhenHua Wang

  3. School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, 02138, USA

    Samir Mitragotri

  4. State Key Laboratory of Marine Environmental Science, College of Ocean & Earth Science, Xiamen University, Xiamen, 361102, China

    Ming Chen

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  1. XueKe Lin
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Correspondence to Ming Chen.

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Lin, X., Wang, Z., Ou, H. et al. Correlations Between Skin Barrier Integrity and Delivery of Hydrophilic Molecules in the Presence of Penetration Enhancers. Pharm Res 37, 100 (2020). https://doi.org/10.1007/s11095-020-02800-4

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