TY - JOUR
T1 - Surfactants from Itaconic Acid: Toxicity to HaCaT keratinocytes in vitro, Micellar Solubilization, and Skin Permeation Enhancement of Hydrocortisone
AU - Abruzzo, Angela
AU - Armenise, Nicola
AU - Bigucci, Federica
AU - Cerchiara, Teresa
AU - Gösser, Mireia Broch
AU - Samori, Chiara
AU - Galletti, Paola
AU - Tagliavini, Emilio
AU - Brown, David McAllister
AU - Johnston, Helinor Jane
AU - Fernandes, Teresa F
AU - Luppi, Barbara
PY - 2017/5/30
Y1 - 2017/5/30
N2 - One of the most widely used approaches for improving drug permeation across the stratum corneum barrier of the skin is the use of chemical penetration enhancers, such as surfactants. In this study, two anionic surfactants, named C12-OPK and C18-OPK, were synthesized via condensation of itaconic acid and fatty amines, with C12 and C18 alkyl chains, respectively. Assessment of impacts on HaCaT keratinocyte cell viability was used as indicator of their potential to cause skin irritation 24 h post exposure (Alamar Blue assay). The LC50 values of C12-OPK and C18-OPK (144 and 85 mg/L, respectively) were lower than LC50 values of the most used commercial surfactants (e.g. SDS). The effect of different surfactant concentrations (up to ten times the critical micellar concentration, CMC) on hydrocortisone (HC) solubility and permeation through porcine skin was also evaluated. Results showed that drug solubility increased linearly with increasing concentrations of both surfactants, as a consequence of the association between drug and micelles. In vitro permeation results showed that the permeability coefficient increased at surfactant concentrations lower than the CMC. In particular, a higher enhancement effect on drug permeation was obtained with C18-OPK, due to its hydrophobic properties that ensured a more effective HC permeation in comparison to C12-OPK.
AB - One of the most widely used approaches for improving drug permeation across the stratum corneum barrier of the skin is the use of chemical penetration enhancers, such as surfactants. In this study, two anionic surfactants, named C12-OPK and C18-OPK, were synthesized via condensation of itaconic acid and fatty amines, with C12 and C18 alkyl chains, respectively. Assessment of impacts on HaCaT keratinocyte cell viability was used as indicator of their potential to cause skin irritation 24 h post exposure (Alamar Blue assay). The LC50 values of C12-OPK and C18-OPK (144 and 85 mg/L, respectively) were lower than LC50 values of the most used commercial surfactants (e.g. SDS). The effect of different surfactant concentrations (up to ten times the critical micellar concentration, CMC) on hydrocortisone (HC) solubility and permeation through porcine skin was also evaluated. Results showed that drug solubility increased linearly with increasing concentrations of both surfactants, as a consequence of the association between drug and micelles. In vitro permeation results showed that the permeability coefficient increased at surfactant concentrations lower than the CMC. In particular, a higher enhancement effect on drug permeation was obtained with C18-OPK, due to its hydrophobic properties that ensured a more effective HC permeation in comparison to C12-OPK.
U2 - 10.1016/j.ijpharm.2017.03.056
DO - 10.1016/j.ijpharm.2017.03.056
M3 - Article
C2 - 28356226
SN - 0378-5173
VL - 524
SP - 9
EP - 15
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -