Development of a phytotherapeutic prototype based on triterpenes encapsulated in nanocarriers for the treatment of obesity and T2DM.

Obesity is fueling a rise in type 2 diabetes mellitus (T2DM), with more than 700 million people worldwide estimated to suffer it by the year 2045 [1]. Previous studies have revealed that a triterpene-rich fraction from Eucalyptus tereticornis leaves reduced fasting blood glucose and improved glucose tolerance and insulin sensitivity in a T2DM murine model by intraperitoneal administration [2], but with limitations across oral administration. This work aimed to develop a polymeric nanocarrier (PN) to transport triterpene-rich fractions orally through the gastrointestinal tract in pre-diabetic mice and control the effects of obesity and T2DM to overcome such limitations.

The PN was formulated with polylactic-co-glycolic acid (PLGA) polymer encapsulating triterpenes, self-assembled by the solvent evaporation method and physicochemically characterized by HPLC, DLS, DSC and SEM. Triterpene release on an in-vitro human gastrointestinal model (GIM), in-vivo assays in a C57BL/6 mouse model, and metabolic biomarkers were assessed, compared and analyzed by ANOVA.

The resultant PN had 165 nm average size, -35,1 zeta potential, 0,18 polydispersity index, 3,5% loading capacity and 98% encapsulation efficiency. The GIM showed a progressive release of triterpenes, lower in the stomach reactor and up to 75% in the intestine. The in-vivo assay demonstrated a decrease in the mice's weight and glucose measured in the blood and changes in metabolic biomarkers related to obesity and T2DM. Overall, these PN administrated orally open the way towards developing new nanoformulations based on natural products to decrease pre-diabetes and obesity in mice with an approximation on human GIM.

Publication History

Article published online:
13 December 2021

• References

• 1 International Diabetes Federation Report, 8th edition, 2017.
• 2 Guillen et al., Adv. Pharmacol. Sci. 418673. 2015.