Recombinant interferon-alpha2b poly（lactic-co-glycolic acid） microspheres： pharmacokinetics-pharmacodynamics study in rhesus monkeys following intramuscular administration  

作　　者：Yong-ming ZHANG Fan YANG Yi-qun YANG Feng-lan SONG An-long XU 

机构地区：[1]State Key Laboratory of Biocontrol, Guangdong Key Laboratory of Pharmaceutical Functional Genes, College of Life Sciences, Sun Yat-Sen University Guangzhou 510275, China [2]Department of Pharmacy, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China [3]School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China

出　　处：《Acta Pharmacologica Sinica》2008年第11期1370-1375,共6页中国药理学报（英文版）

摘　　要：Aim： Investigation into pharmacokinetic-pharmacodynamic properties of interferon-alpha （IFN-α）2b-loaded poly（lactic-co-glycolic acid） （PLGA） microspheres （MS） in rhesus monkey primates. Method： IFN-α2b was loaded with biodegradable PLGA with 3 inherent viscosities using a double emulsion and solvent evaporation method. The particle size, surface morphology, and in vitro release profiles were investigated. Two groups of rhesus monkeys （n=3） were injected intramuscularly with either 3 MIU/kg commercial IFN-α2b lyophilized powder or IFN-α2b-loaded PLGA microspheres （inherent viscosity of 0.89 dL/g）. In vitro release was determined by Lowry protein assay. The serum IFN and neopterin levels were determined by the enzyme-linked immunosorbent assay （ELISA） method to evaluate biological activity of the microspheres in rhesus monkeys. Results： The IFN-α2b microspheres with 3 inherent viscosities （0.39, 0.89, and 1.13 dL/g） were entirely spherical and had a smooth surface. The average diameter of each type was 45.55, 81.23, and 110.25 μm, respectively. The in vitro release was 30 d. The pharmacokinetic-pharmacodynamic properties between the IFN-α2b microspheres and IFN-α2b lyophilized powder were significantly different （P〈0.05）. Conclusion： The drug residence time for the IFN-α2b of the PLGA microsphere with an inherent viscosity of 0.89 dL/g in plasma significantly increased and had a longer time of biological effects in rhesus monkeys following intramuscular administration.Aim： Investigation into pharmacokinetic-pharmacodynamic properties of interferon-alpha （IFN-α）2b-loaded poly（lactic-co-glycolic acid） （PLGA） microspheres （MS） in rhesus monkey primates. Method： IFN-α2b was loaded with biodegradable PLGA with 3 inherent viscosities using a double emulsion and solvent evaporation method. The particle size, surface morphology, and in vitro release profiles were investigated. Two groups of rhesus monkeys （n=3） were injected intramuscularly with either 3 MIU/kg commercial IFN-α2b lyophilized powder or IFN-α2b-loaded PLGA microspheres （inherent viscosity of 0.89 dL/g）. In vitro release was determined by Lowry protein assay. The serum IFN and neopterin levels were determined by the enzyme-linked immunosorbent assay （ELISA） method to evaluate biological activity of the microspheres in rhesus monkeys. Results： The IFN-α2b microspheres with 3 inherent viscosities （0.39, 0.89, and 1.13 dL/g） were entirely spherical and had a smooth surface. The average diameter of each type was 45.55, 81.23, and 110.25 μm, respectively. The in vitro release was 30 d. The pharmacokinetic-pharmacodynamic properties between the IFN-α2b microspheres and IFN-α2b lyophilized powder were significantly different （P〈0.05）. Conclusion： The drug residence time for the IFN-α2b of the PLGA microsphere with an inherent viscosity of 0.89 dL/g in plasma significantly increased and had a longer time of biological effects in rhesus monkeys following intramuscular administration.

关 键 词：interferon-α2b poly（lactic-co-glycolic acid） MICROSPHERES pharmacokinetics and pharmaco-dynamics NEOPTERIN 

分 类 号：R96[医药卫生—药理学]