Prednisolone phosphate-containing TRX-20 liposomes inhibit cytokine and chemokine production in human fibroblast-like synovial cells: a novel approach to rheumatoid arthritis therapy.
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.
Harigai
Takashi
T
Research and Development Center, Terumo Corporation, 1500 Inokuchi, Nakai-machi, Ashigarakamigun, Kanagawa 259-0151, Japan.
Hagiwara
Hitomi
H
Ogawa
Yumi
Y
Ishizuka
Takanobu
T
Kaneda
Shinichi
S
Kimura
Junji
J
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism*; D001550:Benzamidines / Q000008:administration & dosage*; D002478:Cells, Cultured; D005227:Fatty Acids / Q000008:administration & dosage*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008081:Liposomes; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C450860:3,5-dipentadecyloxybenzamidine hydrochloride; D001550:Benzamidines; D005227:Fatty Acids; D015850:Interleukin-6; D016209:Interleukin-8; D008081:Liposomes; D014409:Tumor Necrosis Factor-alpha; C009022:prednisolone phosphate; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011239:Prednisolone