Liposomal targeting of glucocorticoids to synovial lining cells strongly increases therapeutic benefit in collagen type II arthritis.
OBJECTIVE
To investigate the effect of a single intravenous treatment with glucocorticoids (GC) encapsulated in long-circulating PEG-liposomes on both joint inflammation and cartilage destruction and to investigate the phenomenon of selective homing of these liposomes in the inflamed synovium.


METHODS
Mice with collagen type II-induced arthritis (CIA) were intravenously treated with liposomal and free prednisolone phosphate (PLP) a few days after the first signs of the disease. Joint inflammation was scored during 1 week after treatment, after which sections of the knee joints were prepared for assessment of cartilage damage. In addition, arthritic mice were treated with liposomes containing colloidal gold. 24 hours after injection, knee joint sections were prepared in which the location of liposomes was visualised.


RESULTS
Treatment of CIA with 10 mg/kg liposomal PLP resulted in a strong and lasting resolution of joint inflammation. 10 mg/kg free PLP only became slightly effective after repeated daily injections. Although joint inflammation recurred 1 week after treatment with liposomal PLP, knee joint sections prepared at this time indicated that the cartilage damage was still reduced. Localisation of gold labelled liposomes in the inflamed joints was seen in the proximity of blood vessels, in the cellular infiltrate, but mainly in the synovial lining. Unaffected joints did not take up liposomes.


CONCLUSIONS
By using the property of long-circulating liposomes to target the synovial lining selectively in inflamed joints, the anti-inflammatory activity of GC can be greatly increased, showing also the beneficial effect of reduced cartilage destruction.
Metselaar
J M
JM
Department of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences, The Netherlands.
van den Berg
W B
WB
Holthuysen
A E M
AE
Wauben
M H M
MH
Storm
G
G
van Lent
P L E M
PL
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D005938:Glucocorticoids / Q000008:administration & dosage*; D006614:Hindlimb; D007275:Injections, Intravenous; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008081:Liposomes; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D011239:Prednisolone / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D013154:Spleen / Q000473:pathology; D013583:Synovial Membrane / Q000187:drug effects* / Q000473:pathology
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D008081:Liposomes; C009022:prednisolone phosphate; D011239:Prednisolone