Development of interferon alpha-2b microspheres with constant release

Interferon alpha-2b (IFNα-2b) is an important immune regulator used widely in clinic. However, frequent subcutaneous injection and substantial toxicity decrease patients’ compliance. So, drug delivery with more precisely controlled drug release is urgent for IFNα-2b. Microsphere is a promising sustained drug delivery system, which has been studied widely for delivery of proteins. However, it was found difficult to keep proteins’ activity and guarantee complete release. In this study, we solidified IFNα-2b as microparticles firstly by co-lyophilizing it with gelatin and ZnSO4. Microspheres were then prepared. The preparing procedure and formulation were optimized with encapsulation efficiency and in vitro release as main parameters. Finally, the microspheres were prepared by S/O/W method with microparticle size about 5 μm and PEGT/PBT-PLGA (9:1, w/w) as matrix material. The diameter of microspheres was 28.94 μm, the encapsulation efficiency was 86.01%, the burst release was 16.69%, the cumulative release was 83.06% at 23th day, and IFNα-2b was released from microspheres with a zero-order profile. These microspheres also demonstrated sustained and steady release for about 13 days in rats. In conclusion, the procedure and formulation used in this study were supposed to be successful to keep IFNα-2b active and released constantly and completely.

Graphical abstractInterferon alpha-2b was released from microspheres with a zero-order profile except the burst release both in vitro and in vivo.Figure optionsDownload full-size imageDownload as PowerPoint slide