• Journal of Pharmaceutical Investigation
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• v.26 no.4
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• pp.273-280
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• 1996

Chondroitin sulfate/gelatin microspheres containing dexamethasone 21-acetate were prepared by complex coacervation method and their release patterns were examined in vitro. Microspheres prepared with a small amount of crosslinking agent had smooth surface and few pores, but those with a large amount of crosslinking agent were more porous and less spherical. In vitro release patterns were varied by changing polymer/drug weight ratio and amount of crosslinking agent. The release rate of dexamethasone 21-acetate in the presence of collagenase was faster than that in the absence of collagenase. Anti-inflammatory effect of dexamethasone 21-acetate microspheres was more efficient than that of dexamethasone 21-acetate solution in carrageenan-induced arthritis in the rat. On the basis of the above results, we might expect the degradation and drug release rate of these microspheres to be regulated by the degree of crosslinking and the level of enzymes. In patients with severe rheumatoid arthritis who have high concentration of collagenase, more drug would be released from the microspheres. An intra-articular injection therapy of rheumatoid arthritis with desired release kinetics could be developed to enhance patient compliance and therapeutic index.

• Tuberculosis and Respiratory Diseases
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• v.80 no.1
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• pp.60-68
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• 2017

Background: Mucus hypersecretion from airway epithelium is a characteristic feature of airway inflammatory diseases. Tumor necrosis factor ${\alpha}$ (TNF-${\alpha}$) regulates mucin synthesis. Glucocorticoids including mometasone fuorate (MF) have been used to attenuate airway inflammation. However, effects of MF on mucin production have not been reported. Methods: Effects of MF and budesonide (BUD) on the phorbol-12-myristate-13-acetate (PMA)-induction of mucin and TNF-${\alpha}$ in human airway epithelial cells (NCI-H292) were investigated in the present study. Confluent NCI-H292 cells were pretreated with PMA (200 nM) for 2 hours. Subsequently, the cells were stimulated with MF (1-500 ng/mL) or BUD (21.5 ng/mL) for 8 hours. Dexamethasone ($1{\mu}g/mL$) was used as the positive control. Real-time polymerase chain reaction was used to determine MUC2 and MUC5AC mRNA levels. The level of total mucin, MUC2, MUC5AC, and TNF-${\alpha}$ in culture supernatants were measured using enzyme-linked immunosorbent assay. Results: MF and BUD significantly suppressed MUC2 and MUC5AC gene expression in PMA-stimulated NCI-H292 cells. The inhibitory effects of the two steroid drugs were also observed in the production of total mucin, MUC2 and MUC5AC proteins, and TNF-${\alpha}$. Conclusion: Our findings demonstrated that MF and BUD attenuated mucin and TNF-${\alpha}$ production in PMA-induced human airway epithelial cells.