Journal
JOURNAL OF MOLECULAR LIQUIDS
Volume 364, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.molliq.2022.119946
Keywords
Betulinic acid; SNEDDS; Nanoemulsions; Pharmacokinetics; In vitro digestion
Funding
- CONACyT [286926]
- [LN295261]
- [LN254119]
- [LN299082]
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Betulinic acid (BA) is a bioactive molecule with low water solubility. This study developed self-nanoemulsifying drug delivery systems (SNEDDS) to improve the bioavailability of BA. The SNEDDS showed significantly increased bioavailability in both in vitro and in vivo experiments.
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. Pseudoternary phase diagrams were prepared to determine the spontaneous nanoemulsification zone of the systems, using Cremophor EL (R) and Labrafil M1944CS (R) as surfactants. Nanoemulsions with particle sizes ranging from approxi-mately ca. 22 to 56 nm and polydispersity indices of 0.058-0.135 were obtained. The SNEDDS were sub-jected 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, com-pared to free BA.(c) 2022 Elsevier B.V. All rights reserved.
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