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℃ for 24 hr, the steroid encapsulated within liposome hardly leaked out, and of which phase-transition temperature(Tm) was near at 40℃.
$\underline{In vivo}$ studies through λ-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.
Natural glucocorticoid-hydrocortisone- 과 synthetic its analoques-prednisolone, dexamethasone, triamcinolone, methylprednisolone, and paramethasone-등은 강력한 소염작용을 지니나 다량 투여하였을 때 Cushing씨 병과 같은 심한 독 작용을 나타내어 만월상 얼굴 (moon-face appearance), 선조증, 조모증, 갑상선, 기능 저하, 부신 수축등을 유발하는데 가장 심한 전신 증상 으로는 당뇨병의 발생, 고혈압, 심한 감염증에 대한 방어 기능의 장애 등을 들수 있다.
이러한 약용량의 증가 투여로 인해 야기되는 부작용을 극소화시키기 위하여 liposome 을 담체로 한 prednisolone 사용으로 inflamed region 에 효과적인 targeting 을 시도해 보았다. in vitro 상 에서 본 실험에 가장 이상적인 liposome system 으로써 새로이 합성한 prednisolone 유도체인 prednisolone palmitate 5 mg, DPPC 9 mg, 그리고 DHPC 3 mg 으로 확립하고 in vivo test를 행하였다. λ-carrageenan-induced paw edema test 와 cotton pellet granuloma assay 로 부터 liposome 내에 봉입 되어진 상태로 투여한 prednisolone palmitate는 기존의 약물인 prednisolone hemisuccinate in 40% DMSO solution, 또는 methylprednisolone sodium succinate in PBS 보다 훨씬 적은 용량에서 치료 효과를 나타 내었으며, 또한 문제시 되는 부작용인 adrenal atrophy 증상을 제거할 수 있었다.
그러므로 liposome 을 담체로 하여 anti-inflammatory steroids 를 소염 목적으로 투여할 때 병변 진행에 있어서 탐식 세포가 깊이 관련된 rheumatoid arthritis, auto-immune haemolytic anemia, 그리고 idiopathic thrombocytopenic purpurea 등에 효과적인 targeting을 행할 수 있을 것으로 사료되어 진다.
