Modulating meloxicam existing forms in PLGA microspheres to achieve drug sustained release and efficient osteoarthritis treatment.

Poly (lactic-co-glycolic acid) (PLGA) microspheres are widely used for controlled drug delivery, but the drug existing state in the microspheres significantly influences the characteristics of microspheres. The focus of the present study was to formulate meloxicam injectable sustained release microspheres (MLX-MS) and to investigate the influence of the drug existing state within the microspheres on the release properties, degradation and to evaluate the intra-articular (IA) treatment efficacy of osteoarthritis (OA). Different MLX-MS were prepared by changing drug existing forms (microcrystal, particle and molecular state) by the method of cosolvent combination or micronized drug and they were characterized by scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS), X-ray diffraction (XRD) and in vitro release. The therapeutic effect of MLX-MS was investigated using OA rabbits after IA injection. The degradation, drug retention, and pharmacodynamics were also assessed. The results highlighted that the release and degradation of MLX-MS in the joint cavity were directly correlated to the drug existing state. This study offers crucial insights for developing sustained-release injectable MLX-MS, the microspheres with drug existing in molecular state (Mol-MS) were the optimum formulation which can provide sustained release and more effective therapy of joint inflammation.