Release behavior and intra-articular biocompatibility of celecoxib-loaded acetyl-capped PCLA-PEG-PCLA thermogels

In this study, we investigated the invitro and invivo properties and performance of a celecoxib-loaded hydrogel based on a fully acetyl-capped PCLA-PEG-PCLA triblock copolymer. Blends of different compositions of celocoxib, a drug used for pain management in osteoarthritis, and the acetyl-capped PCLA-PEG-PCLA triblock copolymer were mixed with buffer to yield temperature-responsive gelling systems. These systems containing up to 50mg celecoxib/g gel, were sols at room temperature and converted into immobile gels at 37°C. Invitro, release of celecoxib started after a ~10-day lag phase followed by a sustained release of ~90 days. The release was proven to be mediated by polymer dissolution from the gels. Invivo (subcutaneous injection in rats) experiments showed an initial celecoxib release of ~30% during the first 3 days followed by a sustained release of celecoxib for 4-8 weeks. The absence of a lag phase and the faster release seen invivo were likely due to the enhanced celecoxib solubility in biological fluids and active degradation of the gel by macrophages. Finally, intra-articular biocompatibility of the 50mg/g celecoxib-loaded gel was demonstrated using μCT-scanning and histology, where no cartilage or bone changes were observed following injection into the knee joints of healthy rats. In conclusion, this study shows that celecoxib-loaded acetyl-capped PCLA-PEG-PCLA hydrogels form a safe drug delivery platform for sustained intra-articular release.

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