Enhanced bioavailability of betulinic acid using a self-nanoemulsifying drug delivery system (SNEDDS) with fish oil

Abstract

Betulinic acid (BA) is a naturally occurring pentacyclic triterpene compound that exhibits various biological activities such as anticancer, antiviral, anti-inflammatory, anti-hyperlipidemic, and hepatoprotective. Because of its lupane-like chemical structure, this compound exhibits low solubility in aqueous media, leading to low bioavailability and a short half-life in systemic circulation when administered orally. To solve solubility and bioavailability problems, nanotechnology offers the design of encapsulation systems based on lipids, such as self-nanoemulsifying drug delivery systems (SNEDDS). Limited reports show that low-energy techniques prepare betulinic acid encapsulation systems. Therefore, in the present work, the development of SNEDDS is proposed for the encapsulation of betulinic acid using fish oil as the oil phase, Cremophor EL® as surfactant, and Labrafil M1944CS® as co-surfactant. The results showed that fish oil was the one that solubilized more significant amounts of BA (12.96 mg BA/g of oil). The systems with fish oil showed average droplet sizes between 19.44 and 40.33 nm, while the PDI ranged from 0.037 to 0.144 and was allowed to encapsulate from 0.73 to 2.82 mg of BA with 94.1 % encapsulation efficiency. The system evaluated in vitro exhibited no substantial change in particle size throughout the study, but there was a significant change in the polydispersity index (PDI). Finally, in the in vivo evaluation with Wistar rats, a bioavailability of 17 times greater than free betulinic acid was obtained. These results show a significant increase in bioavailability when encapsulating BA using fish oil rich in DHA and EPA, which could be helpful for future applications in the medical field for the treatment of various pathologies such as cancer.