Quantitative Structure-Activity Relationship of Enhancers of Licochalcone A and Glabridin Release and Permeation Enhancement from Carbomer Hydrogel

Abstract

This study aimed to systematically compare licochalcone A (LicA) and glabridin (Gla) (whitening agents) release and permeation from Carbomer 940 (CP) hydrogels with different enhancers, and evaluate the relationship between the quantitative enhancement efficacy and structures of the enhancers. An in vitro release study and an in vitro permeation experiment in solution and hydrogels using porcine skin were performed. We found that the Gla–CP hydrogel showed a higher drug release and skin retention amount than LicA–CP due to the higher solubility in medium and better miscibility with the skin of Gla than that of LicA. Enhancers with a higher molecular weight (MW) and lower polarizability showed a higher release enhancement effect (ERrelease) for both LicA and Gla. The Van der Waals forces in the drug–enhancers–CP system were negatively correlated with the drug release percent. Moreover, enhancers with a higher log P and polarizability displayed a higher retention enhancement effect in solution (ERsolution retention) for LicA and Gla. Enhancers decreased the whole intermolecular forces indrug–enhancers-skin system, which had a linear inhibitory effect on the drug retention. Moreover, C=O of ceramide acted asthe enhancement site for drug permeation. Consequently, Transcutol® P (TP) and propylene glycol (PG), seven enhancers showed a higher retention enhancement effect in hydrogel (ERhydrogel retention) for LicA and Gla. Taken together, the conclusions provide a strategy for reasonable utilization of enhancers and formulation optimization in topical hydrogel whitening.

Log P Determines Licorice Flavonoids Release Behaviors and Classification from CARBOMER Cross-Linked Hydrogel

“…Ten kinds of LFs-CP hydrogels (drug loading: 5%, w / w ) were formulated as follows: LFs monomer compounds in ethanol solution were mixed with Carbomer 940, which was fully swelled in water beforehand, and the mixture was stirred until homogeneous. Finally, the pH was adjusted to 5 with NaOH solution [ 21 , 27 , 28 ]. Hydrogel films were obtained by freeze-dried technique until there was no residual water in the films before analysis.…”

“…The rheological study was conducted using an MARS iQ Air+P35 rheometer (Thermo Scientific HAAKE, New York, NY, USA). Flow properties of the hydrogels were obtained from continuous shear flow tests with the shear rates at 0–120 s −1 for 120 s. The G″ value was measured by frequency sweep tests ranging from 0.1% to 100% strain at constant frequency [ 21 , 27 , 29 ].…”

4′-OH as the Action Site of Lipids and MRP1 for Enhanced Transdermal Delivery of Flavonoids

“…Since Cer took the highest content of the skin lipid, Cer was selected as the skin lipid bilayer model. A lower χ value and higher CED value were indicative of better compatibility and higher intermolecular force between the two. , Gla 1 and Lic B possessed the lowest χ value (1.53 and 6.59 kcal/mol), indicative of better miscibility with the Cer. Thus, Gla 1 and Lic B could form stronger hydrogen-bonding interactions with the skin and belong to the LP-HR drugs.…”

“…The flavonoid compounds Carbomer hydrogels were prepared according to the previous study, , respectively. First, the safety of the hydrogels was investigated by cell adhesion test (Method S5).…”

“…Flavonoids, a class of natural active ingredients, are valuable for both skin health-promoting activities and skin ailments therapeutic benefits owing to their anti-inflammatory, antioxidative, and antiaging pharmacological effects. , For example, liquiritin and isoliquiritin are mainly utilized in atopic dermatitis, skin aging, and photoaging. , Glabridin and licochalcone A , are known skin-whitening agents, which suppress melanin synthesis, while isoliquiritigenin and licochalcone B are efficacious in skin melanoma. Flavonoids share a similar skeleton consisting of a benzene ring linked with a pyrone ring, with varying substitutes to create 9 groups, such as flavone, flavonol, chalcone, dihydrochalcone, etc .…”