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 pm; 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 crosslinker 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. (C) 2011 Elsevier Ltd. All rights reserved.