Biol. Pharm. Bull. 29(7) 1436—1440 (2006)

pressive and anti-inflammatory actions. Most glucocorticoids are administrated repeatedly because of their short half-life and are used for not only continuous treatment but also pulse treatment. However, even at moderate doses, the systemic administration of glucocorticoids causes many side-effects, such as diabetes, hypertension, Cushing syndrome, and osteoporosis. Therefore, it is effective for glucocorticoids to be retained in the blood and delivered to target tissues such as inflammatory tissues and the immune system. Liposomes have various advantages as drug carriers such as biodegradability, low in vivo toxicity, and the encapsulation of hydrophilic, lipophilic and amphipathic drugs. It was reported that long-circulating liposomes of prednisolone phosphate markedly increased the biological activity and reduced side-effects as compared to its solution after intravenous treatment for arthritis and multiple sclerosis. Prednisolone phosphate, however, was difficult to sufficiently incorporate into liposomes because of its high aqueous solubility. Prednisolone (PLS) is a frequently used glucocorticoid in the clinical field. We previously reported that the low incorporation efficiency of PLS was observed in gel filtration although PLS showed high trapping efficiency by liposomes after ultrafiltration. This indicated that PLS was released easily from liposomes by dilution with elution medium in gel filtration. We therefore newly synthesized palmitoyl prednisolone (Pal-PLS) with high lipophilicity, and successfully prepared liposomes completely incorporating Pal-PLS; however, Pal-PLS was withdrawn out of liposomes in the presence of rat plasma. The effect of rat plasma on withdrawing drug out of liposomes was suppressed by using L-a-distearoylphosphatidylcholine (DSPC) and L-a-distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG 2000). Therefore, in this study, we investigated the pharmacokinetic behavior of Pal-PLS and its liposomes with DSPC and cholesterol (Chol) with or without DSPE-PEG 2000 after their intravenous administration in rats.