Prednisolone phosphate-containing TRX-20 liposomes inhibit cytokine and chemokine production in human fibroblast-like synovial cells: a novel approach to rheumatoid arthritis therapy.

Abstract

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.

• Authors: Takashi Harigai, Hitomi Hagiwara, Yumi Ogawa, Takanobu Ishizuka, Shinichi Kaneda, Junji Kimura
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 59 Issue 1 Pg. 137-43 (Jan 2007) ISSN: 0022-3573 [Print] England
• PMID: 17227631 (Publication Type: Journal Article)

Chemical References

• 3,5-dipentadecyloxybenzamidine hydrochloride
• Benzamidines
• Fatty Acids
• Interleukin-6
• Interleukin-8
• Liposomes
• Tumor Necrosis Factor-alpha
• prednisolone phosphate
• Granulocyte-Macrophage Colony-Stimulating Factor
• Prednisolone

Topics

• Adult
• Arthritis, Rheumatoid (drug therapy, metabolism)
• Benzamidines (administration & dosage)
• Cells, Cultured
• Fatty Acids (administration & dosage)
• Female
• Fibroblasts (cytology, metabolism)
• Granulocyte-Macrophage Colony-Stimulating Factor (metabolism)
• Humans
• Interleukin-6 (metabolism)
• Interleukin-8 (metabolism)
• Liposomes
• Middle Aged
• Prednisolone (administration & dosage, analogs & derivatives)
• Synovial Membrane (cytology, metabolism)
• Tumor Necrosis Factor-alpha (pharmacology)