Celecoxib-loaded PLGA/cyclodextrin microspheres: Characterization and evaluation of anti-inflammatory activity on human chondrocyte cultures

• Celecoxib loaded-PLGA/dimethyl-β-cyclodextrin microspheres were prepared.
• Dimethyl-β-cyclodextrin improves technological parameters of PLGA microspheres and modulates the release of celecoxib from the microspheres.
• Celecoxib loaded-PLGA/dimethyl-β-cyclodextrin microspheres was more effective than the free drug as an anti-inflammatory agent on human chondrocyte cultures.
• PLGA/dimethyl-β-cyclodextrin microspheres show good potentiality as delivery systems for the intra-articular administration of CCB.

PLGA microspheres were prepared as a sustained release system for the intra-articular administration of celecoxib (CCB). The microspheres were prepared in the presence of different concentrations of dimethyl-β-cyclodextrin (DM-β-Cyd), by the simple oil-in-water emulsion/evaporation solvent method. The microspheres were evaluated as to surface morphology, size and technological properties (such as encapsulation efficiency, drug loading capacity and drug release). Ex vivo studies on cultures of human chondrocytes were performed in order to evaluate the influence of the polymeric carriers on the pharmacological activity of CCB. All systems ranged from about 1 to 5 μm in size and had a high encapsulation efficiency percentage ranging from about 80% to 90% (w/w), except for CCB-loaded-PLGA microspheres containing the highest amount of DM-β-Cyd, in which a dramatic drop in the encapsulation efficiency was observed (about 54%, w/w). FIB images evidenced the fact that the microspheres had a porous structure in the presence of the highest amount of DM-β-Cyd. The macrocycle modulated the release profiles of CCB from the microspheres, producing in some cases a zero-order kinetic release. Ex vivo biological studies demonstrated that DM-β-Cyd improved the drug's anti-inflammatory activity. Thus, CCB-loaded PLGA/cyclodextrin microspheres may have a potential therapeutic application in the treatment of osteo- and rheumatoid arthritis.

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