Hydroxypropyl-b-cyclodextrin-containing hydrogel enhances
skin formononetin permeation/retention
Paula Hollweg Dias*, Marina Scopel* , Simony Martiny, Sara Elis Bianchi, Valquiria Linck Bassani
e Angelo Silveira Zuanazzi
Programa de P
ao em Ci
euticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
biochanin A; cyclodextrin; formononetin;
high-performance liquid chromatography;
e Angelo Silveira Zuanazzi, Programa de
ao em Ci
Universidade Federal do Rio Grande do Sul,
Porto Alegre, Brazil.
Received August 17, 2017
Accepted March 3, 2018
*Authors contributed equally to this work.
Objectives This study was aimed to investigate the in vitro permeation potential
of hydrogel formulations containing the isoﬂavones formononetin and biochanin
A and cyclodextrins in different combinations.
Methods The permeation assay was performed using porcine skin discs on Franz
diffusion cells model. The isoﬂavone contents of the formulations were quanti-
ﬁed in the different layers of the skin using a validated HPLC-PDA method.
Key ﬁndings The isoﬂavones individually incorporated into the formulations
showed high permeation potential, especially formononetin, after the incorpora-
tion of hydroxypropyl-b-cyclodextrin that enhanced its permeation in the epi-
dermis and dermis. Biochanin A showed 2.7 times of permeation capacity in the
epidermis and dermis mainly after incorporation of cyclodextrins in the formula-
tions. Formononetin showed reduction in its permeation when incorporated in
the formulations together to biochanin A, showing the absence of synergism.
Conclusions Our results indicated a noticeable skin permeation promoting
effect of HPbCD in formononetin formulation. Furthermore, formononetin and
biochanin A can permeate the skin being mostly retained in the epidermis and
dermis, revealing its potential use in cosmetic preparations intended to prevent
Women, after menopause, undergo a drastic reduction in
the production of female hormones, one of the intrinsic fac-
tors of skin aging. This reduction in hormone levels leads to
‘hormone-mediated dermal aging,’ since endogenous estro-
gen could stimulate the production of the structural compo-
nents of the dermis when at normal levels.
Both oral and
topical hormone replacement therapies are alternatives to
maintain the thickness and elasticity of the skin. Isoﬂavones,
due to the similarity to 17-b-estradiol, are strong candidates
for this type of therapy, since they can bind to estrogen
receptors causing beneﬁcial effects on the skin.
Studies have suggested the phytoestrogen-containing
natural sources (e.g. soy) as alternative hormone replace-
ment therapy (HRT) to prevent estrogen-related cardiovas-
cular, menopausal symptoms, osteoporosis and to reduce
the risk of breast cancer from both epidemiological data
and experimental animal studies.
divided into four main groups: ﬂavonoids, coumestans,
mammalian lignans and mainly isoﬂavonoids,
in different source of plants, mainly Leguminosae family,
for example, soy and red clover, with high concentration of
genistein, daidzein, formononetin and biochanin A.
Some studies with topical application of isoﬂavone-agly-
cones such as genistein, daidzein, biochanin A and for-
mononetin have shown their protective effect on the skin
against UV-induced oxidation.
In addition, studies
have conﬁrmed the healing potential of wounds due to the
combined effect of these four isoﬂavones and inhibition of
melanogenesis by biochanin A.
To perform percuta-
neous permeation studies, quantitative determination of
the drug in the skin is necessary aiming the evaluation of its
permeation from the proposed formulations.
no quantiﬁcation studies of formononetin and biochanin A
on different skin layers have been found so far.
The isoﬂavone-aglycone, which has a polyphenolic struc-
ture, has low solubility in water. Studies have shown that in
© 2018 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, 70 (2018), pp. 865–873