Background/Aims: The data available on the skin permeability of ethylhexyl triazone (EHT), a widely used high-molecular-weight (823.1-Da) UV filter, are scarce and obtained only via in vitro studies. Therefore, we evaluated in vivo the penetration of EHT in human stratum corneum by the tape stripping technique. Moreover, the effect of EHT encapsulation in lipid microparticles (LMs) on its diffusion through the stratum corneum was examined. Methods: LMs loaded with EHT were prepared using glyceryl behenate and phosphatidylcholine. Creams containing EHT free or encapsulated in LMs in conjunction with the two most commonly used UV filters, octyl methoxycinnamate (OMC) and butyl methoxydibenzoylmethane (BMDBM), were applied to human volunteers and the fraction of the applied sunscreen dose having penetrated into different stratum corneum layers was measured. Results and Conclusion: For the cream with the nonencapsulated sunscreen agent, the percentage of the applied EHT dose diffused into the stratum corneum was 21.9 ± 4.9%, not significantly different from that of the smaller-molecular-weight OMC (22.2 ± 7.6%) and BMDBM (20.5 ± 3.7%). A marked (45.7%) and statistically significant reduction in the in vivo skin penetration of EHT was attained with the cream containing microencapsulated EHT. The decreased percutaneous penetration provided by the LMs should favor the efficacy of EHT and limit potential toxicological risks.

1.
Lautenschlager
S
,
Wulf
HC
,
Pittelkow
MR
.
Photoprotection
.
Lancet
.
2007
Aug
;
370
(
9586
):
528
37
.
[PubMed]
0140-6736
2.
European Union: Commission recommendation
2006
/647/EC on the efficacy of sunscreen products and the claims made relating thereto. Official J Eur Union 2006;L 265: 39–43.
3.
Hojerová
J
,
Peráčková
Z
,
Beránková
M
.
Margin of safety for two UV filters estimated by in vitro permeation studies mimicking consumer habits: effects of skin shaving and sunscreen reapplication
.
Food Chem Toxicol
.
2017
May
;
103
:
66
78
.
[PubMed]
0278-6915
4.
Puglia
C
,
Damiani
E
,
Offerta
A
,
Rizza
L
,
Tirendi
GG
,
Tarico
MS
, et al
Evaluation of nanostructured lipid carriers (NLC) and nanoemulsions as carriers for UV-filters: characterization, in vitro penetration and photostability studies
.
Eur J Pharm Sci
.
2014
Jan
;
51
:
211
7
.
[PubMed]
0928-0987
5.
Hojerová
J
,
Medovcíková
A
,
Mikula
M
.
Photoprotective efficacy and photostability of fifteen sunscreen products having the same label SPF subjected to natural sunlight
.
Int J Pharm
.
2011
Apr
;
408
(
1-2
):
27
38
.
[PubMed]
0378-5173
6.
Potard
G
,
Laugel
C
,
Schaefer
H
,
Marty
JP
.
The stripping technique: in vitro absorption and penetration of five UV filters on excised fresh human skin
.
Skin Pharmacol Appl Skin Physiol
.
2000
Nov-Dec
;
13
(
6
):
336
44
.
[PubMed]
1422-2868
7.
Chatelain
E
,
Gabard
B
,
Surber
C
.
Skin penetration and sun protection factor of five UV filters: effect of the vehicle
.
Skin Pharmacol Appl Skin Physiol
.
2003
Jan-Feb
;
16
(
1
):
28
35
.
[PubMed]
1422-2868
8.
Scalia
S
,
Mezzena
M
,
Ramaccini
D
.
Encapsulation of the UV filters ethylhexyl methoxycinnamate and butyl methoxydibenzoylmethane in lipid microparticles: effect on in vivo human skin permeation
.
Skin Pharmacol Physiol
.
2011
;
24
(
4
):
182
9
.
[PubMed]
1660-5527
9.
Freitas
JV
,
Praça
FS
,
Bentley
MV
,
Gaspar
LR
.
Trans-resveratrol and beta-carotene from sunscreens penetrate viable skin layers and reduce cutaneous penetration of UV-filters
.
Int J Pharm
.
2015
Apr
;
484
(
1-2
):
131
7
.
[PubMed]
0378-5173
10.
Souza
C
,
Maia Campos
PM
.
Development of a HPLC method for determination of four UV filters in sunscreen and its application to skin penetration studies
.
Biomed Chromatogr
.
2017
Dec
;
31
(
12
):
e4029
.
[PubMed]
0269-3879
11.
Nash
JF
,
Tanner
PR
.
Relevance of UV filter/sunscreen product photostability to human safety
.
Photodermatol Photoimmunol Photomed
.
2014
Apr-Jun
;
30
(
2-3
):
88
95
.
[PubMed]
0905-4383
12.
Hagedorn-Leweke
U
,
Lippold
BC
.
Absorption of sunscreens and other compounds through human skin in vivo: derivation of a method to predict maximum fluxes
.
Pharm Res
.
1995
Sep
;
12
(
9
):
1354
60
.
[PubMed]
0724-8741
13.
Simeoni
S
,
Scalia
S
,
Benson
HA
.
Influence of cyclodextrins on in vitro human skin absorption of the sunscreen, butyl-methoxydibenzoylmethane
.
Int J Pharm
.
2004
Aug
;
280
(
1-2
):
163
71
.
[PubMed]
0378-5173
14.
Golmohammadzadeh
S
,
Jaafarixx
MR
,
Khalili
N
.
Evaluation of liposomal and conventional formulations of octyl methoxycinnamate on human percutaneous absorption using the stripping method
.
J Cosmet Sci
.
2008
Sep-Oct
;
59
(
5
):
385
98
.
[PubMed]
1525-7886
15.
Herzog
B
,
Hueglin
D
,
Osterwalder
U
. New sunscreens actives. In:
Shaath
N
, editor
.
Sunscreens
.
Boca Raton
:
Taylor Francis Group
;
2005
. pp.
293
.
16.
Shi
L
,
Shanb
J
,
Jub
Y
,
Aikens
P
,
Prud’hommea
RK
.
Nanoparticles as delivery vehicles for sunscreen agents
.
Colloids Surf A Physicochem Eng Asp
.
2012
;
396
:
122
9
. 0927-7757
17.
Herzog
B
,
Wehrle
M
,
Quass
K
.
Photostability of UV absorber systems in sunscreens
.
Photochem Photobiol
.
2009
Jul-Aug
;
85
(
4
):
869
78
.
[PubMed]
0031-8655
18.
Lhiaubet-Vallet
V
,
Marin
M
,
Jimenez
O
,
Gorchs
O
,
Trullas
C
,
Miranda
MA
.
Filter-filter interactions. Photostabilization, triplet quenching and reactivity with singlet oxygen
.
Photochem Photobiol Sci
.
2010
Apr
;
9
(
4
):
552
8
.
[PubMed]
1474-905X
19.
Monti
D
,
Brini
I
,
Tampucci
S
,
Chetoni
P
,
Burgalassi
S
,
Paganuzzi
D
, et al
Skin permeation and distribution of two sunscreens: a comparison between reconstituted human skin and hairless rat skin
.
Skin Pharmacol Physiol
.
2008
;
21
(
6
):
318
25
.
[PubMed]
1660-5527
20.
Menon
GK
.
New insights into skin structure: scratching the surface
.
Adv Drug Deliv Rev
.
2002
Nov
;
54
Suppl 1
:
S3
17
.
[PubMed]
0169-409X
21.
Lademann
J
,
Jacobi
U
,
Surber
C
,
Weigmann
HJ
,
Fluhr
JW
.
The tape stripping procedure—evaluation of some critical parameters
.
Eur J Pharm Biopharm
.
2009
Jun
;
72
(
2
):
317
23
.
[PubMed]
0939-6411
22.
Jaspart
S
,
Piel
G
,
Delattre
L
,
Evrard
B
.
Solid lipid microparticles: formulation, preparation, characterisation, drug release and applications
.
Expert Opin Drug Deliv
.
2005
Jan
;
2
(
1
):
75
87
.
[PubMed]
1742-5247
23.
Scalia
S
,
Young
PM
,
Traini
D
.
Solid lipid microparticles as an approach to drug delivery
.
Expert Opin Drug Deliv
.
2015
Apr
;
12
(
4
):
583
99
.
[PubMed]
1742-5247
24.
Simeoni
S
,
Tursilli
R
,
Bianchi
A
,
Scalia
S
.
Assay of common sunscreen agents in suncare products by high-performance liquid chromatography on a cyanopropyl-bonded silica column
.
J Pharm Biomed Anal
.
2005
Jun
;
38
(
2
):
250
5
.
[PubMed]
0731-7085
25.
Scalia
S
,
Trotta
V
,
Iannuccelli
V
,
Bianchi
A
.
Enhancement of in vivo human skin penetration of resveratrol by chitosan-coated lipid microparticles
.
Colloids Surf B Biointerfaces
.
2015
Nov
;
135
:
42
9
.
[PubMed]
0927-7765
26.
Puglia
C
,
Blasi
P
,
Rizza
L
,
Schoubben
A
,
Bonina
F
,
Rossi
C
, et al
Lipid nanoparticles for prolonged topical delivery: an in vitro and in vivo investigation
.
Int J Pharm
.
2008
Jun
;
357
(
1-2
):
295
304
.
[PubMed]
0378-5173
27.
ISO 24443:2012 Determination of sunscreen UVA photoprotection in vitro.
28.
Diffey
BL
,
Robson
J
.
A new substrate to measure sunscreen protection factors throughout the ultraviolet spectrum
.
J Soc Cosmet Chem
.
1989
;
40
:
127
33
.0037-9832
29.
Yue
Y
,
Zhou
H
,
Liu
G
,
Li
Y
,
Yan
Z
,
Duan
M
.
The advantages of a novel CoQ10 delivery system in skin photo-protection
.
Int J Pharm
.
2010
Jun
;
392
(
1-2
):
57
63
.
[PubMed]
0378-5173
30.
Toll
R
,
Jacobi
U
,
Richter
H
,
Lademann
J
,
Schaefer
H
,
Blume-Peytavi
U
.
Penetration profile of microspheres in follicular targeting of terminal hair follicles
.
J Invest Dermatol
.
2004
Jul
;
123
(
1
):
168
76
.
[PubMed]
0022-202X
31.
Milak
S
,
Medlicott
N
,
Tucker
IG
.
Solid lipid microparticles containing loratadine prepared using a Micromixer
.
J Microencapsul
.
2006
Dec
;
23
(
8
):
823
31
.
[PubMed]
0265-2048
32.
Klein
K
,
Palefsky
I
. Formulating sunscreen products. In:
Shaath
N
, editor
.
Sunscreens
.
Boca Raton
:
Taylor Francis Group
;
2005
. p.
356
.
33.
Bonda
CA
. The photostability of organic sunscreen actives: a review; in Shaath N (ed): Sunscreens. Boca Raton, Taylor Francis Group,
2005
, pp 323,334.
34.
Hanno
I
,
Anselmi
C
,
Bouchemal
K
.
Polyamide nanocapsules and nano-emulsions containing Parsol® MCX and Parsol® 1789: in vitro release, ex vivo skin penetration and photo-stability studies
.
Pharm Res
.
2012
Feb
;
29
(
2
):
559
73
.
[PubMed]
0724-8741
35.
Organisation for Economic Cooperation and Development
.
Guidelines for Testing of Chemicals, Guideline 428: Skin Absorption – In vitro Method
.
Paris
:
OECD
;
2004
.
36.
Shah
VP
,
Flynn
GL
,
Yacobi
A
,
Maibach
HI
,
Bon
C
,
Fleischer
NM
, et al
Bioequivalence of topical dermatological dosage forms—methods of evaluation of bioequivalence
.
Pharm Res
.
1998
Feb
;
15
(
2
):
167
71
.
[PubMed]
0724-8741
37.
Weigmann
HJ
,
Lademann
J
,
Schanzer
S
,
Lindemann
U
,
von Pelchrzim
R
,
Schaefer
H
, et al
Correlation of the local distribution of topically applied substances inside the stratum corneum determined by tape-stripping to differences in bioavailability
.
Skin Pharmacol Appl Skin Physiol
.
2001
;
14
Suppl 1
:
98
102
.
[PubMed]
1422-2868
38.
Ferrero
L
,
Pissavini
M
,
Marguerie
S
,
Zastrow
L
.
Sunscreen in vitro spectroscopy: application to UVA protection assessment and correlation with in vivo persistent pigment darkening
.
Int J Cosmet Sci
.
2002
Apr
;
24
(
2
):
63
70
.
[PubMed]
0142-5463
39.
Mavon
A
,
Miquel
C
,
Lejeune
O
,
Payre
B
,
Moretto
P
.
In vitro percutaneous absorption and in vivo stratum corneum distribution of an organic and a mineral sunscreen
.
Skin Pharmacol Physiol
.
2007
;
20
(
1
):
10
20
.
[PubMed]
1660-5527
40.
Sommer
S
,
Wilkinson
SM
,
English
JS
,
Ferguson
J
.
Photoallergic contact dermatitis from the sunscreen octyl triazone
.
Contact Dermat
.
2002
May
;
46
(
5
):
304
5
.
[PubMed]
0105-1873
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.