Controlled release of Celecoxib: an in vitro study with canine degenerated nucleus pulposus cells

Abstract

Introduction- Degeneration of the intervertebral disc (IVD) is a complex process and is known to be a cause of different diseases associated with lower back pain in dogs. Aim of the study- The overall purpose of this project is to translate treatment towards the veterinary patients suffering from lower back pain by a controlled release of medication via local delivery. The hypothesis of this in vitro study is that celecoxib released from a hydro-gel has a sustained anti-inflammatory effect compared to celecoxib bolus treatment on canine degenerated nucleus pulposus cells (NPCs). Materials and methods- Canine NPCs were cultured in pellets and treated with TNF-α to induce inflammation to recreate a situation similar to the in vivo situation of a degenerated IVD. Pellets were treated with celecoxib loaded hydro-gel and different concentrations of celecoxib in bolus form. The effects were evaluated by performing gene measurement, biochemical analysis and histological staining. Results- Pellets treated with TNF-α in qPCR, biochemical and histological analysis showed a decrease of anabolic matrix components (COL2 and ACAN) and an increase of the catabolic components (MMPs and ADAMTS5). Pellets treated with the loaded hydro-gel showed an even further downregulation of the anabolic genes and upregulation of the catabolic genes. Treatment with celecoxib bolus treatment did not show any regenerative effect. Conclusion- No anti-inflammatory effect was shown of celecoxib in this study. Recreating an inflammatory model for an in vitro study to evaluate a treatment of degenerated intervertebral discs is complicated, mainly due to possible dominating effects of TNF-α and a dynamic process of inflammation and regeneration. Data shown in this study were not in line with published data of the use of celecoxib hydro-gel in vivo.