Raman Microscopy and Imaging: Applications to Skin Pharmacology and Wound Healing - Emerging Raman Applications and Techniques in Biomedical and Pharmaceutical Fields - page 369

15.3.2 Vitamin E Acetate Delivery and Metabolism in Skin
by Confocal Raman Microscopy

Introduction

Human skin is frequently exposed to oxidative stress. The resulting damage
is likely an important factor in pathogenesis of skin cancer and photoaging.
Vitamin E (

-TH, structure in Fig. 15.7a), well known for its free radical
scavenging activity, protects biomembranes of cells from peroxidation and
prevents ultraviolet-induced skin damage.
Due to the relative ease of oxidation of the parent compound, common de-
livery forms in cosmetic formulations and clinical trials are vitamin E acetate
(

α

-TAc, structure in Fig. 15.7a) and vitamin E phosphate. These forms are
expected to permeate and to regenerate free active

α

α -TH through enzyme-

catalyzed hydrolysis activities in skin. Although -TAc is readily hydrolyzed

by esterase action to vitamin E upon oral ingestion, no consensus as to the
extent of bioconversion of topically applied

α

-TAc has been reached. Two
published studies demonstrate bioconversion up to 10-15% in the viable epi-
dermis [35] including the basal layer [36]. These and other studies show no
detectable metabolism of

α

-TAc in stratum corneum [37].
The traditional methods for evaluation of the delivery and metabolism
of exogenous materials in skin involve the use of diffusion cells and/or tape
stripping followed by HPLC and mass spectrometry. These methods involve
modification of the skin, provide no spatial information, and may alter skin
transport properties. In this section, both the permeation and metabolism of
α

α

-TAc are monitored inside skin with confocal Raman microscopy.

a

- tocopherolacetate

CH 3

O

59 591

b

c

H 3 C C O

CH 3

200

485

(CH 2 CH 2 CH 2 CH) 3
CH 3

CH 3

560 α TH

H 3 C O

α -TAc

CH 3

CH 3

- tocopherol

HO

CH 3

400 600 800 1000 400 500 600 700 (CH 2 CH 2 CH 2 CH) 3

CH 3

CH 3

Raman shift (cm 1 )

H 3 C O

Raman shift (cm 1 )

CH 3

Fig. 15.7. a Chemical structures of vitamin E (α-TH) and vitamin E acetate
(α-TAc) as indicated. b Confocal Raman spectra of skin after topical application of
60% α-TAc in octanol were acquired every 2 μm to an overall depth of 60 μm. The
first 15 spectra of skin in the 450-1050 cm − 1 range are shown. c Raman spectra of
the 400-700 cm − 1 region for pure vitamin E (α-TH) and pure vitamin E acetate

(α-TAc) as marked