Hypersensitivity reaction studies of a polyethoxylated castor oil-free, liposome-based alternative paclitaxel formulation

The commercial drug paclitaxel (Taxol) may introduce hypersensitivity reactionsassociated with the polyethoxylated castor oil-ethanol solvent. To overcome theseproblems, we developed a polyethoxylated castor oil-free, liposome-based alternativepaclitaxel formulation, known as Lipusu. In this study, we performed in vitroand in vivo experiments to compare the safety profiles of Lipusu and Taxol, withspecial regard to hypersensitivity reactions. First, Swiss mice were used to determinethe lethal dosages, and then to evaluate hypersensitivity reactions, followedby histopathological examination and enzyme-linked immunosorbent assays (ELISAs)of serum SC5b-9 and lung histamine. Additionally, healthy human serum was usedto analyze in vitro complement activation. Finally, an MTT assay was used to determinethe in vitro anti-proliferation activity. Our data clearly showed that Lipusudisplayed a much higher safety margin and did not induce hypersensitivity or hypersensitivity-relatedlung lesions, which may be associated with the fact that Lipusu did not activatecomplement or increase histamine release in vivo. Moreover, Lipusu did not promotecomplement activation in healthy human serum in vitro, and demonstrated anti-proliferativeactivity against human cancer cells, similar to that of Taxol. Therefore, theimproved formulation of paclitaxel, which exhibited a much better safety profileand comparable cytotoxic activity to Taxol, may bring a number of benefits tocancer patients.