IN VIVO DELIVERY OF IL-1RA FROM PLGA MICROSPHERES PREVENTS IL-1B INDUCED GLYCOSAMINOGLYCAN LOSS IN THE RAT CAUDAL INTERVERTEBRAL DISC

摘要

Inflammation plays a central role in the progression of disc degeneration, which is strongly implicated as a cause of low back pain. The objectives of this in vivo study were: first to investigate whether PLGA microspheres could be retained in the disc, and second to test whether IL-1ra delivered from those microspheres could effectively inhibit IL-1β induced extracellular matrix loss using a rat caudal disc model. Three caudal disc levels (C6-7 to C8-9) of 6 Sprague-Dawley rats were exposed via a dorsal midline incision for treatment. Fluorescently labeled microspheres were clearly visible in the disc at all time points except 8 weeks. The GAG content of discs injected with IL-1β alone was significantly lower than that of the intact controls and the microsphere treatment group. For discs injected with both IL-1β and IL-1ra microspheres, GAG content was not different from the intact control. In this study we demonstrated for the first time that IL-1ra delivered from microspheres prevents IL-1β induced GAG loss in vivo, and that microspheres are retained in the disc space for at least 4 weeks.