title: Enhanced oral bioavailability of acetylpuerarin by poly(lactide-co-glycolide) nanoparticles optimized using uniform design combined with response surface methodology.
abstract: 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.
authors.affiliation: Department of Pharmacy, the Second Hospital of Shandong University, Jinan, People's Republic of China; School of Pharmaceutical Sciences, Shandong University, Jinan, People's Republic of China.
authors.forename: Deqing
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Cardiology, the Second Hospital of Shandong University, Jinan, People's Republic of China.
authors.forename: Aiying
authors.initials: A
authors.lastname: Xue
authors.affiliation: Department of Pharmacy, the Second Hospital of Shandong University, Jinan, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, the Second Hospital of Shandong University, Jinan, People's Republic of China.
authors.forename: Xia
authors.initials: X
authors.lastname: Xue
authors.affiliation: Department of Pharmacy, the Second Hospital of Shandong University, Jinan, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, the Second Hospital of Shandong University, Jinan, People's Republic of China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D015195:Drug Design; D007529:Isoflavones / Q000737:chemistry / Q000493:pharmacokinetics*; D008968:Molecular Conformation; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011098:Polyglactin 910 / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties
chemical_list: D007529:Isoflavones; C521069:acetylpuerarin; D011098:Polyglactin 910
keywords: acetylpuerarin; bioavailability; nanoparticles; pharmacokinetics; poly(lactic-co-glycolic acid)