Formulation, biological and pharmacokinetic studies of sucrose ester-stabilized nanosuspensions of oleanolic Acid.

PURPOSE

The aim of this study was to develop sucrose ester (SE)-stabilized oleanolic acid (OA) nanosuspensions (NS) for enhanced delivery.

METHODS

SEOA NS were prepared via O/W emulsion and organic solvent evaporation methods. The particles' size and polydispersity index were measured by nanosizer. Their percent encapsulation efficiency, saturation solubility and in vitro dissolution rate were obtained via HPLC. The in vitro bioefficacy was analyzed by MTT measurements in A549 human non-small-cell lung cancer cell line. The cellular uptake of OA and in vivo pharmacokinetics profile were determined using LC-ESI-MS/MS.

RESULTS

Spherical SEOA NS particles (~100 nm in diameter) were produced and found to be physicochemically stable over a month at 4°C. In particular, SEOA 4121 NS (SEL: SEP at 4:1 w/w; SE: OA at 2:1 w/w) produced the greatest increase in saturation solubility (1.89 mg/mL vs. 3.43 μg/mL), dissolution rate, cytotoxicity and bioavailability. Preliminary studies indicated that cellular uptake of SEOA NS by A549 cells was temperature-, concentration- and time-dependent.

CONCLUSION

Preparing OA as SE-stabilized NS particles provides a novel method to enhance saturation solubility, in vitro dissolution rate, bioefficacy and in vivo bioavailability of free OA and/or other potentially useful hydrophobic drugs.