Use of liposome as a carrier of a novel anti-inflammatory agent prednisolone palmitate

Abstract

To decrease toxicity, degradation, and bioinactivation of prednisolone and its derivative being used as an anti-inflammatory agent, they are encapsulated within a liposome as a carrier in order to bring, in a controlled fashion, them into effective contact with the target. For preparation of liposomes, egg phosphatidylcholine(PC), sphingomyelin(SM), cholesterol, dipalmitoyl phosphatidylcholine (DPPC), diheptadecanoyl phosphatidylcholine(DHPC), distearoyl phosphatidylcholine (DSPC), and egg phosphatidic acid(PA) were examined. In order to increase the degree of incorporation, and retention of prednisolone toward vesicles, prednisolone palmitate was newly synthesized. When 5 mg of a newly synthesized prednisolone palmitate was used in order to prepare liposomes consisting of 9 mg of DPPC, and 3 mg of DHPC by the method of vortexing and sonication, the incorporation efficiency was 71\%. In addition, when they are incubated at $37\,^\circ\!C$ for 24 hr, the steroid encapsulated within liposome hardly leaked out, and of which phase-transition temperature(Tm) was near at $40\,^\circ\!C$. In vivo studies through $\lambda$-carrageenan paw edema test and cotton pellet granuloma assay to compare the antiinflammatory activity of prednisolone palmitate encapsulated within liposomes with that of free steroid prednisolone hemisuccinate in 40\% dimethylsulfoxide(DMSO) solution or methylprednisolone sodium succinate in phosphate-buffered saline(PBS) suggested that prednisolone palmitate encapsulated within liposomes resulted in a stronger antiinflammatory activity and showed little influence upon adrenal glands than the free steroids used did.