Self-nanoemulsifying drug delivery system (SNEDDS) improves the oral bioavailability of betulinic acid

Betulinic acid (BA) is a bioactive molecule with antineoplastic, antiviral, anti-inflammatory features; however, it exhibits low solubility in water, which limits its practical applications. Our work aims to develop self-nanoemulsifying drug delivery systems (SNEDDS) to improve the bioavailability of BA. We found that the oil phases containing Lauroglycol FCC and caprylic acid solubilized the greatest amount of the bioactive with 15.8 ± 0.089 and 16.019 ± 0.11 mg/mL, respectively.

Highlights

Caprylic acid and Lauroglycol FCC enable greater solubility of betulinic acid.

Cremophor EL and Labrafil M1944CS form SNEDDS with different oils.

The SNEDDS show a high resistance to in vitro digestion conditions.

SNEDDS increase the bioavailability of betulinic acid administered orally.

Pseudoternary phase diagrams were prepared to determine the spontaneous nanoemulsification zone of the systems, using Cremophor EL® and Labrafil M1944CS® as surfactants. Nanoemulsions with particle sizes ranging from approximately ca. 22 to 56 nm and polydispersity indices of 0.058–0.135 were obtained. The SNEDDS were subjected to in vitro gastrointestinal conditions, where the particle size of the nanosystems remained constant up to 105 min of simulated small intestine phase conditions. The in vivo study in a Wistar rat model demonstrated up to a 15-fold increase in BA bioavailability when administered in SNEDDS, compared to free BA.

Diego A. Bravo-Alfaro, Laura R. Ochoa-Rodríguez, Francisco Villaseñor-Ortega, Gabriel Luna-Barcenas, Hugo S. García, Self-nanoemulsifying drug delivery system (SNEDDS) improves the oral bioavailability of betulinic acid, Journal of Molecular Liquids, Volume 364, 2022, 119946, ISSN 0167-7322,
https://doi.org/10.1016/j.molliq.2022.119946.

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