Study on preparation and pharmacokinetics of rhein-loaded polylactic acid nanoparticles / 中国药学杂志

ABSTRACT

OBJECTIVE: To prepare rhein-loaded polylactic acid nanoparticles, and investigate their physicochemical properties, release behavior in vitro and pharmacokinetics in vivo in rats. METHODS: Rhein-loaded polylactic acid nanoparticles were prepared by a modified spontaneous emulsificationsolvent diffusion method with PLA as the carrier. The morphology of rhein-loaded polylactic acid nanoparticles was observed by transmission electron microscope. Mean particle size and Zeta potential were estimated by laser particle size analyzer. Entrapment efficiency and drug loading were investigated by ultracentrifugation. Drug release behavior in vitro was studied by dialysis. Using rhein aqueous suspension as control, the pharmacokinetic behavior of rhein-loaded polylactic acid nanoparticles after oral administration in rats were studied. RESULTS: The shape of rhein-loaded polylactic acid nanoparticles was spherical. The mean particle size, Zeta potential, entrapment efficiency and drug loading were (134.37 ± 3.61) nm, (-18.41 ± 0.07) mV, (60.37 ± 1.52)% and (1.32 ± 0.09)%, respectively. The profiles of release were fitted well by Higuchi equation. Results of pharmacokinetic study showed that the ρmax of rhein suspension and rhein-loaded polylactic acid nanoparticles were (5.788 ±0.15) and (11.607 ± 0.56) mg · L-1, tmax were (0.193 ±0.01) and (1.102 ±0.13) h, AUC0→t were(8.077 ±2.98) and (34.583 ±3.93) mg · h · L-1, t1/2β were (3.319 ±0.23) and (21.721 ± 6.13) h, respectively. CONCLUSION: Polylactic acid nanoparticles can effectively improve the pharmacokinetic behaviour and oral bioavailability of rhein. Copyright 2012 by the Chinese Pharmaceutical Association.