Glucocorticoids in nano-liposomes administered intravenously and subcutaneously to adjuvant arthritis rats are superior to the free drugs in suppressing arthritis and inflammatory cytokines.
We have previously shown that intravenous (i.v.) treatment with sterically stabilized nano-liposomes (NSSL) actively remote-loaded with the glucocorticoid (GC) methylprednisolone hemisuccinate (NSSL-MPS) or betamethasone hemisuccinate (NSSL-BMS) significantly decreased severity of adjuvant arthritis in Lewis rats (a model of human rheumatoid arthritis) throughout all disease stages. Here, we compared i.v. or subcutaneous (s.c.) weekly treatment with each of the two NSSL-GC to weekly or daily treatment with the free drugs or with the TNF-α antagonists Infliximab and Etanercept. Therapeutic efficacy and effects on the profile of pro-inflammatory (IL-6, TNF-α, and INF-γ) and anti-inflammatory (IL-10 and TGF-β) cytokines in rat sera and splenocyte tissue culture supernatants were compared to those of the liposomal and free drugs. Both s.c. and i.v. NSSL-GC suppressed arthritis significantly, compared to higher doses of the free drugs or to TNF-α antagonists. NSSL-GC also suppressed the secretion of pro-inflammatory cytokines, but did not change the levels of TGF- β. The highly efficacious anti-inflammatory therapeutic feature of these nano-drugs makes them candidates for treatment of human rheumatoid arthritis.
Hadassah University Hospital, Jerusalem, Israel.
Rina
R
Ulmansky
Keren
K
Turjeman
Moshe
M
Baru
Galia
G
Katzavian
Michal
M
Harel
Alex
A
Sigal
Yaakov
Y
Naparstek
Yechezkel
Y
Barenholz
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D001623:Betamethasone / Q000008:administration & dosage / Q000627:therapeutic use; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood*; D004334:Drug Administration Schedule; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008081:Liposomes; D008776:Methylprednisolone Hemisuccinate / Q000008:administration & dosage / Q000627:therapeutic use; D051379:Mice; D008815:Mice, Inbred Strains; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004337:Drug Carriers; D005938:Glucocorticoids; D008081:Liposomes; D008776:Methylprednisolone Hemisuccinate; D001623:Betamethasone