Protein loaded CA-gel／PLGA composite microspheres were prepared by a novel SPG membrane emulsification method

which was modified from the traditional preparation method of PLGA microspheres. The formation of the sustainedrelease gel was based on the ionic interaction between Sa and calcium ion. The drug loading of composite microspheres was significantly increased from 6.94% to 8.35%

entrapment efficiency was increased from 62.47% to 75.16%，and the burst release rate was declined from 42.32% to 30.84%. Drug release test showed that nearly 40.29% of drug was continuously and steadily released from the composite microspheres in 2~40 days. The drug release curves were corresponded to Peppas-Sahlin equation (R

2

>

0.99) for both the traditional microspheres and composite microspheres

which means that the release mechanism was mainly diffusion and dissolution. The results from scanning electron microscopy and freezing microtomy demonstrated that the composite microspheres were more compact in structure

and its surface hole number and porosity were smaller than traditional PLGA microspheres. The enhanced fluorescence intensity was observed from the laser confocal scan microscopy

  indicating that more protein drugs were wrapped inside composite microspheres. In conclusion

the CA-gel／PLGA composite microspheres can effectively increase drug loading and entrapment efficiency and reduce the burst release.