| Interferon-alpha (IFN-α) is a multifunctional cytokine. In addition to anti-viral activity, it also has effects of inhibiting the growth of tumor cells and regulating the immune function, is widely used in clinical treatment of viral diseases and cancers, and is the first drug for anti-virus therapy of hepatitis B and C. But as the half-life of IFN-αis short, long-term frequent injection is needed, resulting in large fluctuation of plasma concentration, limited effects and relatively more side effects. Therefore, development of a kind of sustained release injection of IFN-αis urgently needed.IFNα-2b injectabe microspheres were prepared by the double emulsion(W/O/W) solvent evaporation method with Poly(lactic acid-co-glycolic acid) (PLGA) as carriers in this study. First, in vitro release of IFNα-2b microspheres of different formulations were studied. Second, the pharmacokinetics of IFNα-2b microspheres following intramuscular administration in rats was studied to evaluate the formulations of IFNα-2b microspheres.According to the IFN microspheres preparation process of our patent, IFNα-2b microspheres were obtained by using different viscosities and concentrations PLGA along with IFNα-2b, and their In vitro release were studied. IFNα-2b microspheres of 0.89dL/g -15% PLGA had good release profiles within 30 days.In pharmacokinetics study on IFNα-2b microspheres after intramuscular administration in rats, following characteristics were revealed: The pharmacokinetics of three doses of IFNα-2b injection resembles two-compartment model. The pharmacokinetics of IFNα-2b injection (market-approved injectable IFNα-2b lyophilized powder) microspheres with different viscosities and concentrations of PLGA (0.89dL/g -15%, 0.89dL/g -20% and 1.13dL/g -15% PLGA) showed that there was no significant differences of peak time (Tmax), peak concentration (Cmax), area under curve (AUC), and mean residence time (MRT) (P>0.05). The pharmacokinetics of three doses (0.5MIU, 1MIU, 2MIU) of microspheres loading IFNα-2b stock solution were compared. Results showed the Cmax were linear related with the injected doses(r=0.9997). Following single administration of 2MIU IFNα-2b microspheres, Tmax, Cmax, AUC, and MRT were 12h, 5329.88pg/ml, 192084(pg/ml)*h, and 146.40h, respectively. The microspheres had sustained–release characteristics with a long release term of 21 days in vivo. Following single administration of 0.5MIU IFNα-2b injection, injection microspheres and stock solution microspheres (both microspheres with 0.89dL/g -15% PLGA), the pharmacokinetic parameters were as follows: Tmax were 0.75, 1.5, 8.0 and 12.0h; Cmax were 5889.82, 1275.34 and 1404.09pg/ml; MRT were 2.19, 38.49 and 122.33h; AUC were 1294.70, 22278.6 and 71096.14 (pg/ml)*h, respectively.In short, our IFNα-2b microspheres with 0.89dL/g -15% PLGA loading stock solution had good pharmacokinetics in rats. The study would be helpful references for other scholars.
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