Modulation of chemical dermal absorption by 14 natural products: a quantitative structure permeation analysis of components often found in topical preparations.
A large number of cosmetics and topical pharmaceuticals contain compounds of natural origin. There is a rising concern if these compounds can interact with the activity of other topically applied components in these formulations. The current study demonstrates modulation of dermal absorption of model components often found in topical preparations (14C caffeine and14C salicylic acid) by a set of 14 compounds of natural origin using a flow through in vitro porcine skin diffusion system. The parameters of flux and permeability were calculated and quantitative structure permeation relationship (QSPR) analysis conducted on different molecular descriptors of modulator compounds. Terpinyl acetate was the greatest permeability/flux enhancer for caffeine followed by s-perillyl acetate and limonene 1,2-epoxide. The permeability/flux of salicylic acid was highest with hydroxycitronellal followed by limonene 1,2-epoxide and s-perillyl acetate. The optimum descriptors using stepwise regression analysis for predicting additive modulation on penetrant permeability/flux were polar surface area, log P for caffeine and Henry's Law constant, number of freely rotatable bonds, and water solubility for salicylic acid. In parallel with the experimental techniques, a novel mathematical model was developed to estimate the permeability coefficients and improve the stepwise regression analysis for assessing modulator effects. The r2values significantly increased for multicomponent QSPR models. Notably, limonene 1,2-epoxide and s-perillyl acetate were excellent enhancers for both caffeine and salicylic acid. These results confirm that some natural products incorporated into topical formulations will enhance absorption of other components which could affect their safety and efficacy profiles.
a Institute of Computational Comparative Medicine, Kansas State University , Manhattan , KS , USA.|b Department of Anatomy and Physiology , Kansas State University , Manhattan , KS , USA.
Faqir
F
Muhammad
a Institute of Computational Comparative Medicine, Kansas State University , Manhattan , KS , USA.|c Department of Mathematics , Kansas State University , Manhattan , KS , USA , and.
Majid
M
Jaberi-Douraki
d Department of Pharmaceutical Sciences , Federal University of Paraiba , João Pessoa, Paraiba , Brazil.
Damião Pergentino
DP
de Sousa
a Institute of Computational Comparative Medicine, Kansas State University , Manhattan , KS , USA.|b Department of Anatomy and Physiology , Kansas State University , Manhattan , KS , USA.
Jim E
JE
Riviere
D000287:Administration, Topical; D000818:Animals; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D002110:Caffeine / Q000737:chemistry / Q000493:pharmacokinetics*; D003358:Cosmetics / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D066298:In Vitro Techniques; D008954:Models, Biological; D010539:Permeability; D021281:Quantitative Structure-Activity Relationship; D020156:Salicylic Acid / Q000737:chemistry / Q000493:pharmacokinetics*; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D013552:Swine
D001688:Biological Products; D003358:Cosmetics; D002110:Caffeine; D020156:Salicylic Acid
Absorption; QSPR; compounds of natural origin; mathematical modeling; mixtures; skin