Studies on Pharmacokinetics of Recombinant Human Interferon-alphα-2b Microspheres in Rats
|School||Guangdong College of Pharmacy|
|Keywords||IFNα-2b Poly lactic acid - glycolic acid Microspheres Pharmacokinetics|
Interferon α (Interferon-alpha, IFN-α) is a multifunctional cytokine, in addition to having antiviral activity, also inhibit the growth of tumor cells that regulate the immune function of clinical virus has been widely used in treatment of diseases and tumors, the first-line treatment of hepatitis B and hepatitis C antiviral therapy. However, interferon α half-life is short, and long-term frequent injections, leading to large fluctuations in the plasma concentration, the efficacy is limited and the side effects of a relatively large. Thus, of interferon α long-acting injections developed much scholarly attention. In this paper, this laboratory patented process (a complex milk (W / O / W) solvent evaporation method) IFNα-2b, recombinant human injectable sustained release microspheres were prepared in vitro effects of different prescription IFNα-2b microspheres release drug characteristics, IFNα-2b microspheres in rats in vivo pharmacokinetic characteristics, and through the main pharmacokinetic parameters between evaluation of microspheres prescription. First microsphere preparation process patents in the lab already, prepared different viscosity and concentration of PLGA IFNα-2b microspheres were investigated in vitro release characteristics of the microspheres prepared. The results show that the viscosity 0.89dL / g, prepared IFNα-2b concentration of 15% PLGA microspheres burst effect is small, can be slow-release 30 days, has good release characteristics in vitro. Pharmacokinetic study in rats, the control group rats intramuscular injection of three doses (0.5 MIU MIU 2MIU) IFNα-2b pharmacokinetic study results show that the commercially available powder injection: IFNα-2b meet the two-compartment model pharmacokinetic properties in rats. Second compared 0.89dL/g-15 of%, 0.89dL/g-20%, 1.13dL/g-15% PLGA of IFNα-2b powder for injection microsphere sustained-release effect in rats. The results show that: the main pharmacokinetic parameters - blood concentration peak time (T max ), the peak concentration (C max ), the mean residence time (MRT) and drugs The area under the curve (AUC) There was no significant difference (P gt; 0.05). Third, compare the The intramuscular injection 0.5MIU IFNα-2b powder for injection and IFNα-2b powder for injection microspheres dope microspheres (two microspheres prescription for 0.89dL/g-15% PLGA) in rats The sustained-release effect. The results showed that: between any two of the microsphere group significant difference (P lt; 0.05), the microspheres powder injection group had very significant difference (P lt; 0.01). Fourth, the relatively 0.89dL/g-15% PLGA IFNα-2b stock solution of microspheres 0.5MIU 1MIU 2MIU three doses in rats in vivo pharmacokinetic characteristics. The results showed: C max and the injected dose was linear correlation (r = 0.9997), after a single intramuscular injection of the microspheres preparation 2MIU IFNα-2b T max 12h , C max 5329.88pg/ml AUC was 192084 (pg / ml) * h, MRT for 146.40h blood concentration can be maintained for 21 days. The rat single intramuscular injection 0.5MIU IFNα-2b powder for injection and after two microspheres the T max for 0.75,1.5,12.0 h and; C max for 5889.82 , 1275.34,1404.09 pg / ml; MRT for 2.19,38.49,122.33 h; AUC 11294.70,22278.6,71096.14 (pg / ml) * h. The results show that prepared by the method used by this laboratory Patent 0.89dL/g-15% PLGA IFNα-2b dope microspheres having a better sustained release effect in rats. This study for peptide, protein drugs microsphere formulations developed to provide a meaningful reference for.