METANOB

Artículos científicos

• Reboredo C, González-Navarro CJ, Martínez-López AL, Irache JM. Oral administration of zein-based nanoparticles reduces glycemia and improves glucose tolerance in rats. Int J Pharm. 2022; 628:122255. https://doi.org/10.1016/j.ijpharm.2022.122255. PMID: 36191813.
• Campión R, Gonzalez-Navarro CJ, Luisa Martínez López A, et al. Zein-based nanospheres and nanocapsules for the encapsulation and oral delivery of quercetin. Int J Pharm. 2023; 643: 123216. https://doi.org/10.1016/j.ijpharm.2023.123216. PMID: 37423375

Patente

• Reboredo C., Martínez-López, A.L, González-Navarro C.J., Vizmanos, J.L., Irache, J.M., inventors. Zein nanoparticles for use in hyperglycemic conditions. UNAV. Priority EP20383153.2 (12/01/2021). Publication WO2022136393A1 (30/06/2022).

Tesis

• Campión Rodríguez, Raquel. “Improvement of the bioavailability of quercetin encapsulated in zein-based nanoparticles. Effects on a Diet-Induced Obesity model”. Irache, J.M. y González-Navarro, C.J. (dirs.). Tesis doctoral. Programa de Doctorado: Medicamentos y Salud. Universidad de Navarra, Pamplona, 25/11/2022. Calificación: Cum laude.

Obesity is a serious public health problem that has reached epidemic proportions in many countries and its derived health and social costs are very significant. Furthermore, the risk of developing insulin resistance, dyslipidemia, fatty liver disease, hypertension and diverse coronary diseases increases considerably in obese people. Thus, identifying and characterising new bioactive compounds with a natural origin that can be added to food or administered as nutraceuticals is extremely interesting to limit and, to a certain degree, counteract the undesirable effects associated with obesity or being overweight.

Nevertheless, many of the bioactive compounds with a potential use for preventing diseases are not absorbed well. Furthermore, those unabsorbed compounds can be transformed by the microbiota creating metabolites that may themselves be bioactive. That means the effectiveness of the compounds depends on diverse factors that may affect the microbiota, like diet or some diseases.

To those ends, the activity of two series of compounds that include a bioactive, its precursor and a metabolite produced by the microbiota action have been evaluated in the first project year. A C. elegans screening model that we have extensive experience with was used for the evaluations. With the model we can evaluate the reduction of accumulated fat after administering the compounds.
In a previous project it was corroborated that the action of the bacterial metabolism modifies the biological effect of the compounds tested, confirming the hypothesis that that effect can be influenced by the metabolic action of colon bacteria. And the two compounds with the greatest fat reducing effect in a C elegans model were chosen, which are the ones that were tested in this project.

Subsequently, and after evaluating the pharmacokinetics of the compounds chosen to determine their bioavailability, we studied their effectiveness for different parameters associated with obesity (for example glycaemia), administered via parenteral route, which is to say when their activity is not limited by intestinal absorption or other factors associated with oral administration, as could occur in a functional complement or food.

In parallel, various kinds of nanoparticles based on a food grade protein with different properties were developed by coating the surface of the nanoparticles with polymers that let the encapsulated compound reach specific areas of the intestines. It was thus possible to control whether the encapsulated compound is absorbed in the small intestine or, on the contrary, it travels to the large intestine and is released in that area.

These new formulations were tested in a mammal model with diet induced obesity to determine whether the changes in bioavailability that occur when the compounds are formulated in nanoparticles improves their effectiveness.

The results show that encapsulation of one of the bioactive compounds chosen using different kinds of nanoparticles improves the bioavailability of the compound. On the other hand, some of the formulations developed showed significant improvements in several parameters and indices related with obesity and metabolic syndrome, like a lower percentage of visceral and subcutaneous body fat, a new improvement in the plasma triglyceride levels and an improvement in inflammation markers. Likewise, one of the treatments improved glycaemia and the response on the glucose tolerance curve, indicating an improvement in glucose metabolism in animals.

The results of the project open up new avenues for research into the development of nutraceuticals that can help prevent or mitigate the effects of obesity and the associated comorbidities.