Study on Stability of Staphylokinase Variant (K35R) Loaded Poly (lactic-co-glycolic acid) Microspheres

OBJECTIVE To investigate the status of a staphylokinase variant (K35R,DGR) loaded microspheres and the main factors that influence the stability of encapsulated DGR.METHODS Fourier transform infrared (FT-IR) spectroscopy was used to examine the secondary structure of DGR encapsulated in Poly(lactic-co-glycolic acid) (PLGA) microspheres. The influence of pH and adsorption of PLGA surface on the stability of DGR was evaluated. RESULTS The second structure of encapsulated DGR changed significantly.The stability of DGR was not influenced by the change. SDS-PAGE analysis of PLGA microspheres showed that dimeric and polymeric DGR formed after being released for 20 d. Mg(OH)2 nanoparticles coencapsulated with DGR inhibited the aggregation of DGR within microspheres during release.Acidic microclimate within microspheres was an important source for the denaturation of encapsulated DGR. Research on adsorption of DGR to PLGA showed that non-specific adsorption of DGR to PLGA by hydrophobic and ionic interaction were also potential sources,which leaded to the denaturation of DGR within microspheres.CONCLUSION The second structure of DGR is significantly changed by the microencapsulation. However,the change of the second structure don′t influence the stability of encapsulated DGR. The main factors resulting in the denaturation of encapsulates DGR included the acidic microenvironment and non-specific adsorption of DGR to PLGA surface.