Retention and distribution of liposome-entrapped [3H]methotrexate injected into normal or arthritic rabbit joints.
Normal or arthritic rabbits were injected intra-articularly (i.a.) with free [3H]methotrexate ([3H]MTX) or liposomes containing [3H]MTX with [14C]cholesteryl oleate as a lipid marker. The distribution of 3H and 14C in the injected joint and other tissues was determined. Free [3H]MTX was rapidly cleared from the joint, 79% being excreted in the urine within 24 h of injection. Liposome-entrapment retarded [3H]MTX clearance from the joint (P less than 0.001), 45.5% being recovered from the joint 24 h after injection. Uptake of liposomes by the inflamed synovium was lower than expected, 4% liposomal [3H]MTX injected being associated with the synovium after 24 h. Nevertheless, this was 40-fold greater than when free [3H]MTX was injected. Liposome entrapment should improve the efficacy and reduce the side effects of drugs injected directly into the joint cavity.
Foong
W C
WC
School of Pharmacy and Biomedical Sciences, Portsmouth Polytechnic, UK.
Green
K L
KL
D000818:Animals; D001168:Arthritis / Q000378:metabolism*; D001169:Arthritis, Experimental / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002788:Cholesterol Esters / Q000493:pharmacokinetics; D007596:Joints / Q000378:metabolism*; D008081:Liposomes / Q000008:administration & dosage*; D008727:Methotrexate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits; D012016:Reference Values; D014018:Tissue Distribution; D014316:Tritium
D002250:Carbon Radioisotopes; D002788:Cholesterol Esters; D008081:Liposomes; D014316:Tritium; C014409:cholesteryl oleate; D008727:Methotrexate