Fabrication of core–shell microspheres using alginate and chitosan–polycaprolactone for controlled release of vascular endothelial growth factor

Alginate microspheres loaded with vascular endothelial growth factor (VEGF) were prepared via an emulsification method using calcium chloride as a crosslinker. The microspheres with encapsulation efficiency of about 80% were coated by chitosan–polycaprolactone (CH–PCL) with various PCL percentages changing from around 15 to 42   wt.% to fabricate core–shell alginate/CH–PCL microspheres with an average size of around 40   μm. It was found that the CH–PCL coating layer on the core–shell microspheres could have a sandwich-like structure. The PCL content in the CH–PCLs and the concentration of CH–PCL solutions in preparing the microsphere functioned as two key factors to regulate the release profiles of the microspheres. Some selected alginate/CH–PCL microspheres were further crosslinked using genipin as a crosslinker, and the amount of genipin was found to be another impactful factor to mediate the release patterns of the microspheres. In vitro release measurements revealed that VEGF-release from these core–shell microspheres was controlled either by Fickian diffusion or non-Fickian transport that involves both diffusion and swelling. Some optimized core–shell microspheres were capable of maintaining sustained VEGF-release in an approximately linear manner over a period of time longer than 4   weeks and did not involve a significant initial burst.