Preparation of nanoparticles of ZL-004 and preliminary study on its pharmacokinetics / 中国药学杂志

ABSTRACT

OBJECTIVE: To prepare ZL-004 loaded PLGA nanoparticles (ZL-004-NP) and evaluate its release characteristics in vitro and pharmacokinetics in rats. METHODS: In order to determine physico-chemical property of ZL-004, saturation-constant temperature method, potentiometric method and shake flask method were employed to obtain relative parameters, respectively. After investigating single factors, the orthogonal design was used to gain optimal formulation. Then characteristic of ZL-004-NP prepared under condition of best formulation was determined by scanning electronmicroscopy, laser particle size analyzer, dialysis method, respectively. Afterward, amounts of ZL-004 in plasma were determined under UPLC-MS/MS and relative bioavailability between ZL-004-NP and its raw material was calculated. RESULTS: The feature of ZL-004-NP met aim of experiment, which contained smooth spheres, 121.34 nm of diameter, 0.16 of PDI, 89.63% of encapsulation efficiency, 7.65% of loading drug content, sustained release about 216 h in vitro and less burst in initiate stage. In vivo, cmax of ZL-004-NP was increased robustly 1.7 times, which reached to 125 μg · L-1 and tmax was cut down rapidly from (6.47 ± 0.51) h to (4.13 ± 0.48) h, compared with crude ZL-004. Relative bioavailability between ZL-004-NP and crude ZL-004 was 200.99%, which greatly improved effect of oral absorption. CONCLUSION: ZL-004-NP might be developed to improve water-insolube nature of ZL-004, which could increase oral relative bioavailability.