Prednisolone phosphate-containing TRX-20 liposomes inhibit cytokine and chemokine production in human fibroblast-like synovial cells: a novel approach to rheumatoid arthritis therapy
| Autor: | Shinichi Kaneda, Hitomi Hagiwara, Junji Kimura, Yumi Ogawa, Takashi Harigai, Takanobu Ishizuka |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Chemokine animal structures medicine.medical_treatment Prednisolone Pharmaceutical Science Pharmacology Proinflammatory cytokine Arthritis Rheumatoid Medicine Macrophage Humans Interleukin 8 Interleukin 6 Cells Cultured Liposome biology business.industry Interleukin-6 Tumor Necrosis Factor-alpha Fatty Acids Interleukin-8 Synovial Membrane Granulocyte-Macrophage Colony-Stimulating Factor Fibroblasts Middle Aged Benzamidines Cytokine Biochemistry Drug delivery Liposomes biology.protein Female business |
| Zdroj: | The Journal of pharmacy and pharmacology. 59(1) |
| ISSN: | 0022-3573 |
| Popis: | To evaluate the potential of using prednisolone phosphate (PSLP)-containing 3,5-dipentadecyloxybenzamidine hydrochloride (TRX-20) liposomes to treat rheumatoid arthritis (RA), we examined their ability to bind human fibroblast-like synovial (HFLS) cells and their effects in these cells. To test for binding, Lissamine rhodamine B-1, 2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine (rhodamine)-labelled PSLP-containing TRX-20 liposomes were added to HFLS cells, and the fluorescence intensity of the rhodamine bound to the cells was evaluated. Rhodamine-labelled PSLP-containing liposomes without TRX-20 were used as a negative control. To evaluate the uptake of liposomes by the HFLS cells, we used TRX-20 liposomes containing 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS) and p-xylene-bis-pyridinium bromide (DPX), and observed the cells by fluorescence microscopy. The effects of the PSLP in TRX-20 liposomes on HFLS cells were assessed by the inhibition of the production of two inflammatory cytokines (interleukin 6 and granulocyte macrophage colony-stimulating factor) and one inflammatory chemokine (interleukin 8). The interaction of the PSLP-containing TRX-20 liposomes with HFLS cells was approximately 40 times greater than that of PSLP-containing liposomes without TRX-20. PSLP-containing TRX-20 liposomes bound to HFLS cells primarily via chondroitin sulfate. TRX-20 liposomes taken up by the cell were localized to acidic compartments. Furthermore, the PSLP-containing TRX-20 liposomes inhibited the production of the inflammatory cytokines and the chemokine more effectively than did the PSLP-containing liposomes without TRX-20. These results indicate that PSLP-containing TRX-20 liposomes show promise as a novel drug delivery system that could enhance the clinical use of glucocorticoids for treating RA. |
| Databáze: | OpenAIRE |
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