Dexamethasone palmitate (DMP) entrapped in liposomes of defined sizes was administered intraarticularly in healthy rabbits and in rabbits with antigen-induced arthritis. The pharmacokinetics and therapeutic effect of liposomal DMP were measured and compared with corresponding experiments using microcrystalline triamcinolone acetonide (TAC). The small DMP liposomes (diameter 160 nm) showed a greater decrease in joint circumference than the 3-times-higher dose of microcrystalline TAC. Moreover, about 98% of administered TAC had already disappeared from the joint 6 h after injection, whereas about 36% of liposomal DMP was still measured in synovial fluid and synovium at the same time. Increasing the vesicle diameter from 160 to 750 nm (large liposomes) improved the retention of DMP by a factor of 2.6 within 48 h after injection in healthy rabbits. In addition, none of the liposomal glucocorticoid preparations ever suppressed the endogenous plasma cortisol level, which is in contrast to the suppression measured after administration of the microcrystalline preparation.

The fate of oligolamellar and multilamellar vesicles containing dexamethasone palmitate after intra-articular injection into healthy rabbit joints was investigated to improve the liposome formulation in respect to better bioavailability of the effective substance within the arthritic joint. The defined negatively charged oligolamellar vesicles (dexamethasone) palmitate, egg phosphatidylcholine, phosphatidic acid, molar ratio 0.24:10.1) of a mean diameter of 0.75 micron gave better results than multilamellar vesicles (dexamethasone palmitate, dipalmitoylphosphatidylcholine, phosphatidic acid, molar ratio 0.24:10:1) used for the same purpose by several other authors. The positive charge carrier stearylamine does not induce any improvement.

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