Imaging Drug Delivery to Skin with Coherent Raman Scattering Microscopy

  • Natalie A. Belsey
  • Luis Rodrigo Contreras-Rojas
  • Richard H. Guy


Coherent Raman scattering microscopy is a new technique allowing high-resolution 3D imaging of the skin, with chemical contrast obtained based on Raman scattering. This technique is label-free and, unlike conventional microscopy techniques, does not rely on fluorescent probes, which are not good models for drug substances because of their different physicochemical properties and dissimilar skin penetration kinetics. Unlike other techniques such as tape stripping, coherent Raman scattering microscopy is non-destructive. The penetration pathway(s) of the drug and excipients from a topical vehicle can be visualised independently, and the ‘metamorphosis’ of an applied formulation at the surface of the skin can be imaged in real time.


Stratum Corneum Propylene Glycol Stimulate Raman Scattering Skin Lipid Intercellular Lipid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Coherent anti-Stokes Raman scattering




Dimethyl sulfoxide




Fourier transform infrared spectroscopy


High-performance liquid chromatoraphy


Lock-in amplifier




Objective lens




Retinoic acid


Stimulated Raman gain


Stimulated Raman loss


Stimulated Raman scattering


  1. 1.
    Herkenne C, Alberti I, Naik A, Kalia YN, Mathy FX, Preat V et al (2008) In vivo methods for the assessment of topical drug bioavailability. Pharm Res 25(1):87–103PubMedCrossRefGoogle Scholar
  2. 2.
    Pawley J (ed) (2006) Handbook of biological confocal microscopy, 3rd edn. Springer, New YorkGoogle Scholar
  3. 3.
    Potts RO, Guy RH (1992) Predicting skin permeability. Pharm Res 9(5):663–669PubMedCrossRefGoogle Scholar
  4. 4.
    Dias M, Naik A, Guy RH, Hadgraft J, Lane ME (2008) In vivo infrared spectroscopy studies of alkanol effects on human skin. Eur J Pharm Biopharm 69(3):1171–1175PubMedCrossRefGoogle Scholar
  5. 5.
    Hanh BD, Neubert RHH, Wartewig S, Christ A, Hentzsch C (2000) Drug penetration as studied by non invasive methods: Fourier transform infrared-attenuated total reflection, Fourier transform infrared, and ultraviolet photoacoustic spectroscopy. J Pharm Sci 89(9):1106–1113PubMedCrossRefGoogle Scholar
  6. 6.
    Foerster M, Bolzinger M-A, Ach D, Montagnac G, Briancon S (2011) Ingredients tracking of cosmetic formulations in the skin: a confocal Raman microscopy investigation. Pharm Res 28(4):858–872CrossRefGoogle Scholar
  7. 7.
    Caspers PJ, Lucassen GW, Carter EA, Bruining HA, Puppels GJ (2001) In vivo confocal Raman microspectroscopy of the skin: non invasive determination of molecular concentration profiles. J Invest Dermatol 116(3):434–442PubMedCrossRefGoogle Scholar
  8. 8.
    Pudney PDA, Melot M, Caspers PJ, van der Pol A, Puppels GJ (2007) An in vivo confocal Raman study of the delivery of trans-retinol to the skin. Appl Spectrosc 61(8):804–811PubMedCrossRefGoogle Scholar
  9. 9.
    Forster M, Bolzinger M-A, Montagnac G, Briancon S (2011) Confocal Raman microspectroscopy of the skin. Eur J Dermatol 21(6):851–863PubMedGoogle Scholar
  10. 10.
    Bonnist EYM, Gorce JP, Mackay C, Pendlington RU, Pudney PDA (2011) Measuring the penetration of a skin sensitizer and its delivery vehicles simultaneously with confocal Raman spectroscopy. Skin Pharmacol Physiol 24(5):274–283PubMedCrossRefGoogle Scholar
  11. 11.
    Freudiger CW, Min W, Saar BG, Lu S, Holtom GR, He C et al (2008) Label-free biomedical imaging with high sensitivity by stimulated Raman scattering microscopy. Science 322(5909):1857–1861PubMedCrossRefGoogle Scholar
  12. 12.
    Saar BG, Freudiger CW, Reichman J, Stanley CM, Holtom GR, Xie XS (2010) Video-rate molecular imaging in vivo with stimulated Raman scattering. Science 330(6009):1368–1370PubMedCrossRefGoogle Scholar
  13. 13.
    Saar BG, Contreras-Rojas LR, Xie XS, Guy RH (2011) Imaging drug delivery to skin with stimulated Raman scattering microscopy. Mol Pharm 8(3):969–975PubMedCrossRefGoogle Scholar
  14. 14.
    Raman CV, Krishnan KS (1928) A new type of secondary radiation. Nature 121(3048):501–502CrossRefGoogle Scholar
  15. 15.
    Raman CV, Krishnan KS (1928) The optical analogue of the compton effect. Nature 121(3053):711CrossRefGoogle Scholar
  16. 16.
    Atkins P (1998) Physical chemistry, 6th edn. Oxford University Press, Oxford, UKGoogle Scholar
  17. 17.
    Min W, Freudiger CW, Lu S, Xie XS (2011) Coherent nonlinear optical imaging: beyond fluorescence microscopy. Annu Rev Phys Chem 62:507–30PubMedCrossRefGoogle Scholar

Copyright information

© Springer Berlin Heidelberg 2014

Authors and Affiliations

  • Natalie A. Belsey
    • 1
  • Luis Rodrigo Contreras-Rojas
    • 1
  • Richard H. Guy
    • 1
  1. 1.Department of Pharmacy and PharmacologyUniversity of BathClaverton Down BathUK

Personalised recommendations