Acta Pharmacologica Sinica 2008 November; 29 (11): 1370-1375; doi: 10.1111/j.1745-7254.2008.00881.x

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.

Methods: 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.

Keywords: interferon-α2b; poly(lactic-co-glycolic acid); microspheres; pharmacokinetics and pharmacodynamics; neopterin