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Acetylpuerarin (AP), an acetylated derivative of puerarin, shows brain-protective effects in animals. However, AP has low oral bioavailability because of its poor water solubility. The objective of this study was to design and develop poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) to enhance the oral bioavailability of AP. The NPs were prepared using a solvent diffusion method optimized via uniform design (UD) combined with response surface methodology (RSM) and characterized by their morphology, particle size, zeta (ζ)-potential, encapsulation efficiency (EE), drug loading (DL), and in vitro drug release. A pharmacokinetic study was conducted in Wistar rats administered a single oral dose of 30 mg/kg AP. The optimized NPs were spherical and uniform in shape, with an average particle size of 145.0 nm, a polydispersity index (PI) of 0.153, and a ζ-potential of -14.81 mV. The release of AP from the PLGA NPs showed an initial burst release followed by a sustained release, following Higuchi's model. The EE and DL determined in the experiments were 90.51% and 17.07%, respectively. The area under the plasma concentration-time curve (AUC0-∞) of AP-PLGA-NPs was 6,175.66±350.31 h ng/mL, which was 2.75 times greater than that obtained from an AP suspension. This study showed that PLGA NPs can significantly enhance the oral bioavailability of AP.

drug design, development and therapy

Enhanced oral bioavailability of acetylpuerarin by poly(lactide-co-glycolide) nanoparticles optimized using uniform design combined with response surface methodology