Chitosan-polycaprolactone microspheres as carriers for delivering glial cell line-derived neurotrophic factor

Chitosan-polycaprolactone (CH-PCL) copolymers with brush-like chain structures were synthesized. Some CH-PCLs with a PCL content less than 50 wt% were used to build glial cell line-derived neurotrophic factor (GDNF)-loaded microspheres via an emulsification method using genipin as a cross-linker. The resulting microspheres were spherical with a smooth surface and a diameter less than 40 μm; however, their loading efficiency could be higher than 80% if crosslinked properly. These microspheres had various swelling characteristics in lysozyme-containing PBS, which mainly depended on the PCL content, and they did not exhibit significant degradation up to 3 weeks. It is found that the PCL content in the CH-PCLs predominantly governed GDNF releases from some optimal microspheres and that the amount of cross-linker imposed limited impacts on the release behavior. Release kinetics revealed that GDNF release from microspheres was controlled by anomalous mechanisms involving Fickian diffusion and case-II transport. Some microspheres with an initial loading ratio of approximately 5-ng GDNF to 1.0-mg dry microsphere had sustained GDNF release upon addition of a simulant in vivo medium; an approximate linear rate of release was observed, which lasted over 4 weeks, was controllable and did not involve a significant burst release.