Open AccessRecombinant interferon‐alpha2b poly(lactic‐co‐glycolic acid) microspheres: pharmacokinetics‐pharmacodynamics study in rhesus monkeys following intramuscular administration 1
Author(s) -
ZHANG Yongming,
YANG Fan,
YANG Yiqun,
SONG Fenglan,
XU Anlong
Publication year - 2008
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2008.00881.x
Subject(s) - pharmacokinetics , pharmacodynamics , glycolic acid , plga , pharmacology , chemistry , microsphere , in vitro , chromatography , lactic acid , biochemistry , medicine , biology , chemical engineering , bacteria , engineering , genetics
Aim: Investigation into pharmacokinetic‐pharmacodynamic properties of inter‐feron‐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 MlU/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 urn, 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.