Chitosan-Polylactide/Hyaluronic Acid Complex Microspheres as Carriers for Controlled Release of Bioactive Transforming Growth Factor-β1.

Chitosan(CH)-polylactide(PLA) copolymers containing varied PLA percentages were synthesized using a group-protection method and one of them with solubility in water-based solvents was used to prepare CH-PLA/hyaluronic acid (HA) complex microspheres for the delivery of transforming growth factor-β1 (TGF-β1). An emulsification processing method was developed for producing TGF-β1-loaded CH-PLA/HA microspheres using sodium tripolyphosphate (TPP) as ionic crosslinker and the size of the microspheres was devised to the micron level in order to achieve high encapsulating efficiency. The encapsulating efficiency, swelling property and release administration of the microspheres could be synergistically regulated by PLA component, the applied TPP dose and the incorporated HA amount. In comparison to CH/HA microspheres, the CH-PLA/HA microspheres had greatly reduced TGF-β1 release rates and were able to administrate the TGF-β1 release at controlled rates over a significant longer period of time. The released TGF-β1 was detected to be bioactive when compared to the free TGF-β1. These results suggest that the presently developed CH-PLA/HA complex microspheres have promising potential in delivering TGF-β1 for cartilage repair applications where the applied TGF-β1 amount in the early stage needs to be low whilst the sustained TGF-β1 release at an appropriate dose in the later stage has to be maintained.