Development of chondroitin sulfate encapsulated PLGA microsphere delivery systems with controllable multiple burst releases for treating osteoarthritis.

The purpose of the study was to design and develop unique drug delivery systems with controllable multiple burst releases of drugs for treating osteoarthritis. Chondroitin sulfate (CS) was encapsulated into four types of PLGA materials, that is, PLGA 50:50, PLGA 65:35, PLGA 75:25, and PLGA 85:15. The effects of microsphere size and various combinations of blend PLGA microspheres on CS release were investigated. The cytotoxicity of the CS-encapsulated microspheres was investigated according to the ISO 10993 guideline. Our study showed that the encapsulation efficiency of CS into PLGA 50:50 microspheres varied with the size of microspheres; however, the encapsulation efficiencies of CS into PLGA microspheres were independent of the types of PLGA materials. The size of PLGA microspheres was shown to affect the rate of CS release. With the increase of microsphere size from 75-150 μm to 300-355 μm, the initial CS release decreased. Further increase in microsphere size led to an increase in the initial CS release. In addition, combination of different types of PLGA microspheres was shown to be capable of achieving multiple burst CS releases. Moreover, the CS encapsulated PLGA microspheres were shown to be non-cytotoxic. This study proved the concept of multiple burst drug releases that were achieved by encapsulating CS into different types of PLGA microspheres and delivering CS from systems consisting of mixed types of PLGA microspheres, which may be applied to treat osteoarthritis by mimicking multiple intra-joint injection of therapeutic agents.