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

Wang,Hongbo; Cheng,Guang; Du,Yuan; Ye,Liang; Chen,Wenzhong; Zhang,Leiming; Wang,Tian; Tian,Jingwei; Fu,Fenghua

doi:10.3892/mmr.2013.1264

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

Authors:
- Hongbo Wang
- Guang Cheng
- Yuan Du
- Liang Ye
- Wenzhong Chen
- Leiming Zhang
- Tian Wang
- Jingwei Tian
- Fenghua Fu
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Affiliations: Key Laboratory of Molecular Pharmacology and Drug Evaluation (Ministry of Education of China), School of Pharmacy, Yantai University, Yantai 264005, P.R. China, R&D Center, Nanjing Luye Sike Pharmaceutical Co., Ltd, Nanjing 210061, P.R. China, State Key Laboratory of Long-Acting and Targeting Drug Delivery Technologies (Luye Pharma Group Ltd.), Yantai 264003, P.R. China
Published online on: January 4, 2013 https://doi.org/10.3892/mmr.2013.1264
Pages: 947-952
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The commercial drug paclitaxel (Taxol) may introduce hypersensitivity reactions associated with the polyethoxylated castor oil-ethanol solvent. To overcome these problems, we developed a polyethoxylated castor oil-free, liposome-based alternative paclitaxel formulation, known as Lipusu. In this study, we performed in vitro and in vivo experiments to compare the safety profiles of Lipusu and Taxol, with special regard to hypersensitivity reactions. First, Swiss mice were used to determine the lethal dosages, and then to evaluate hypersensitivity reactions, followed by histopathological examination and enzyme-linked immunosorbent assays (ELISAs) of serum SC5b-9 and lung histamine. Additionally, healthy human serum was used to analyze in vitro complement activation. Finally, an MTT assay was used to determine the in vitro anti-proliferation activity. Our data clearly showed that Lipusu displayed a much higher safety margin and did not induce hypersensitivity or hypersensitivity-related lung lesions, which may be associated with the fact that Lipusu did not activate complement or increase histamine release in vivo. Moreover, Lipusu did not promote complement activation in healthy human serum in vitro, and demonstrated anti-proliferative activity against human cancer cells, similar to that of Taxol. Therefore, the improved formulation of paclitaxel, which exhibited a much better safety profile and comparable cytotoxic activity to Taxol, may bring a number of benefits to cancer patients.

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