RESUMEN
Birch outer bark extract (BBE), containing pentacyclic triterpenes such as betulin, lupeol, and betulinic acid, is a widely recognized natural product renowned for its diverse pharmacological effects. However, its limited water solubility restricts its bioavailability. Therefore, the main objective is to enhance the bioavailability of BBE for pharmaceutical use. In this study, we aimed to develop a dispersion system utilizing a unique oleogel-producing method through the recrystallization of BBE from an ethanol solution in the oil phase. We generated an oleogel that demonstrates a notable 42-80-fold improvement in betulin and lupeol peroral bioavailability from BBE in Wistar rats, respectively. A physical paste-like BBE hydrogel developed with antisolvent precipitation showed a 16-56-fold increase in the bioavailability of betulin and lupeol from BBE in rat blood plasma, respectively. We also observed that the repeated administration of the BBE oleogel did not exhibit any toxicity at the tested dose (38.5 mg/kg betulin, 5.2 mg/kg lupeol, 1.5 mg/kg betulinic acid daily for 7 days). Betulin and betulinic acid were not detected in rat heart, liver, kidney, or brain tissues after the peroral administration of the oleogel daily for 7 days. Lupeol was found in rat heart, liver, and kidney tissues.
RESUMEN
Structuring liquid oils into oleogels using natural and abundant biomass components as gelling agents is of great significance in fields such as foods, pharmaceuticals, and cosmetics. In this work, a more energy-efficient and technologically simpler approach for directly preparing birch outer bark extract particles containing oleogel was used. This method involves introducing birch outer bark extract particles into the oil phase directly from the extract solution, combining both the evaporation of solution and gel formation. As a result, stable oleogels of various vegetable oils (sunflower, almond, olive, and hemp seed) were obtained with birch outer bark extract particle contents of 4-10%. Infrared spectroscopy and particle size analysis confirmed that when increasing the content of extract particles in the oil, increasing self-assembly of extract particles via hydrogen bonding occurs, leading to the formation of a more structured network. This is consistent with gel strength values from rheological tests of oleogels, which also increased with particle concentration. The obtained oleogels showed important properties such as good tolerance to time-dependent deformation, shear thinning, and thermoreversibility.
RESUMEN
The aim of the study was to obtain untreated and treated betulin colloidal particles and assess their effect on the viability, morphology, proliferation and cytokine secretion of human dermal fibroblasts. To improve bioavailability, betulin treatment was performed by an antisolvent precipitation technique. The average particle size after treatment in the aqueous dispersion decreased from 552.9 ± 11.3 to 278.2 ± 1.6 nm. Treated betulin colloidal particles showed no cytotoxicity up to a concentration of 400 µg·mL-1 in the colorimetric tetrazolium salt viability test (CCK-8). Moreover, the cell morphology was not changed in the presence of betulin colloidal particles at a concentration range from 0.78 to 400 µg·mL-1. The obtained results also show that betulin particles induce the secretion of the proinflammatory and angiogenesis-stimulating cytokine IL-8. However, further studies would be required to clarify the mechanism of IL-8 secretion induction.