Development and Evaluation of Khellin-loaded Microemulgel for Dermatological Applications.

Microemulsions are optically nanosized emulsions, isotropic and thermodynamically stable. They represent versatile drug delivery systems with high potential because they can be administered regardless of route. In the present study, we report on the formulation of a microemulsion made with glycerol (2.25%), Labrasol (20.25%) vitamin E acetate (2.50%), and water (75.00%), which was developed using the pseudo-ternary phase diagram. Globules of the microemulsion had PdI less than 0.25 and size of about 17 nm, evaluated by DLS analysis. These values did not change after loading khellin, a natural lipophilic molecule with interesting biological activities, used as a model of lipophilic drug. Carboxymethyl cellulose was selected as gelling polymer to obtain a microemulgel. Viscosity was 22 100.0 ± 1555.6 mPas·s at 21 ± 2 °C, while it was 8916.5 ± 118.1 mPas·s at 35 ± 2 °C, remaining stable over time. Khellin recovery was 93.16 ± 4.39% and was unchanged after 4 weeks of storage (93.23 ± 2.14%). The pH was 6.59 ± 0.19 and it was found to be 6.42 ± 0.34 at the end of the storage lifetime. The diffusion of khellin from the developed formulation was prolonged over an extended period. Based on overall results and due to the dermatological properties of the ingredients of the formulation, the developed microemulgel loaded with khellin is very promising and suitable for skin care applications.

Nanostructured Lipid Carriers Can Enhance Oral Absorption of Khellin, a Natural Pleiotropic Molecule.

A novel formulation based on nanostructured lipid carriers (NLCs) was developed to increase solubility and intestinal absorption of khellin. K-NLCs were prepared with stearic acid, hempseed oil, Brij S20, and Labrafil M 1944 CS, using the emulsification-ultrasonication method. Developed nanoparticles were chemically and physically characterized by liquid chromatography, light scattering techniques, and electron microscopy. The size, about 200 nm, was optimal for oral delivery, and the polydispersity index (around 0.26), indicated high sample homogeneity. Additionally, K-NLCs showed a spherical morphology without aggregation by microscopic analysis. The encapsulation efficiency of khellin was about 55%. In vitro release studies were carried out in media with different pH to mimic physiological conditions. K-NLCs were found to be physically stable in the simulated gastric and intestinal fluids, and they preserved about 70% of khellin after 6 h incubation. K-NLCs were also successfully lyophilized testing different lyoprotectants, and obtained freeze-dried K-NLCs demonstrated good shelf life over a month. Lastly, permeability studies on Caco-2 cells were performed to predict khellin passive diffusion across the intestinal epithelium, demonstrating that nanoparticles increased khellin permeability by more than two orders of magnitude. Accordingly, developed NLCs loaded with khellin represent a versatile formulation with good biopharmaceutical properties for oral administration, possibly enhancing khellin's bioavailability and therapeutic effects.