Long-circulating liposomes of indomethacin in arthritic rats--a biodisposition study.

摘要

To improve the targeting efficiency of liposomes of indomethacin to the arthritic joints, circulation half-life of the liposomes was increased by grafting amphipathic polyethylene glycol-2000 to the bilayer surface. A comparative biodistribution study was performed between the conventional liposomes (PC:CH:PE--1:0.5:0.16) and long-circulating liposomes (PC:CH:PE-PEG--1:0.5:0.16) in arthritic rats. Pharmacokinetics of the drug changed significantly when administered in liposomal form. Pharmacokinetic parameters of the drug such as AUC0-t (trapezoidal), clearance and t1/2 (elimination half-life) changed significantly (p < 0.05) when encapsulated in liposomes. Significant difference in pharmacokinetics was observed in AUC0-t and clearance between the conventional liposomes and long-circulating liposomes. The increased AUC0-t and reduced clearance of the drug with long-circulating liposomes, increased the availability of the drug by reducing RES uptake, in turn localization in arthritic paw tissue was also increased. A concentration of 0.33 microgram of indomethacin/g of the tissue was achieved with S-liposomes after 24 h whereas it was only 0.26 microgram of drug/g of the tissue with conventional liposomes. From the study, in may be concluded that the targeting efficiency of the long-circulating liposomes was about four times more than the conventional liposomes.