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Imaging Drug Delivery to Skin with Stimulated Raman Scattering Microscopy

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Brian G. Saar†, L. Rodrigo Contreras-Rojas

, X. Sunney Xie*†, and Richard H. Guy*

^† Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, United States

Department of Pharmacy & Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, U.K.

Mol. Pharmaceutics, 2011, 8 (3), pp 969–975

DOI: 10.1021/mp200122w

Publication Date (Web): May 6, 2011

*R.H.G.: University of Bath, Department of Pharmacy & Pharmacology, Claverton Down, Bath, BA2 7AY, U.K.; e-mail, r.h.guy@bath.ac.uk; tel, +44.1225.384901; fax, +44.1225.386114. X.S.X.: xie@chemistry.harvard.edu.

‡ Author Contributions

Equal contributors.

§ Author Present Address

MIT Lincoln Laboratory, 244 Wood Street, Lexington, MA 02420.

Abstract

Efficient drug delivery to the skin is essential for the treatment of major dermatologic diseases, such as eczema, psoriasis and acne. However, many compounds penetrate the skin barrier poorly and require optimized formulations to ensure their bioavailability. Here, stimulated Raman scattering (SRS) microscopy, a recently developed, label-free chemical imaging tool, is used to acquire high resolution images of multiple chemical components of a topical formulation as it penetrates into mammalian skin. This technique uniquely provides label-free, nondestructive, three-dimensional images with high spatiotemporal resolution. It reveals novel features of (trans)dermal drug delivery in the tissue environment: different rates of drug penetration via hair follicles as compared to the intercellular pathway across the stratum corneum are directly observed, and the precipitation of drug crystals on the skin surface is visualized after the percutaneous penetration of the cosolvent excipient in the formulation. The high speed three-dimensional imaging capability of SRS thus reveals features that cannot be seen with other techniques, providing both kinetic information and mechanistic insight into the (trans)dermal drug delivery process.

Keywords:

skin; topical drug delivery; stimulated Raman scattering microscopy; skin penetration pathways; dermatopharmacokinetics

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