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

March 2013 Volume 7 Issue 3

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

March 2013 Volume 7 Issue 3

Full Size Image

Article Open Access

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
View Affiliations / Copyright

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

Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
Pages: 947-952
|
Published online on: January 4, 2013

https://doi.org/10.3892/mmr.2013.1264
Expand metrics +

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.

View Figures

View References

1	Jordan MA and Wilson L: Microtubules as a target for anticancer drugs. Nat Rev Cancer. 4:253–265. 2004. View Article : Google Scholar : PubMed/NCBI
2	Kavallaris M: Microtubules and resistance to tubulin-binding agents. Nat Rev Cancer. 10:194–204. 2010. View Article : Google Scholar : PubMed/NCBI
3	Adams JD, Flora KP, Goldspiel BR, Wilson JW, Arbuck SG and Finley R: Taxol: a history of pharmaceutical development and current pharmaceutical concerns. J Natl Cancer Inst Monogr. 141–147. 1993.PubMed/NCBI
4	Szebeni J, Muggia FM and Alving CR: Complement activation by Cremophor EL as a possible contributor to hypersensitivity to paclitaxel: an in vitro study. J Natl Cancer Inst. 90:300–306. 1998. View Article : Google Scholar : PubMed/NCBI
5	Rowinsky EK, Eisenhauer EA, Chaudhry V, Arbuck SG and Donehower RC: Clinical toxicities encountered with paclitaxel (Taxol). Semin Oncol. 20:1–15. 1993.PubMed/NCBI
6	Weiszhar Z, Czucz J, Revesz C, Rosivall L, Szebeni J and Rozsnyay Z: Complement activation by polyethoxylated pharmaceutical surfactants: Cremophor-EL, Tween-80 and Tween-20. Eur J Pharm Sci. 45:492–498. 2012. View Article : Google Scholar : PubMed/NCBI
7	Hennenfent KL and Govindan R: Novel formulations of taxanes: a review. Old wine in a new bottle? Ann Oncol. 17:735–749. 2006. View Article : Google Scholar : PubMed/NCBI
8	Koudelka S and Turanek J: Liposomal paclitaxel formulations. J Control Release. 163:322–334. 2012. View Article : Google Scholar : PubMed/NCBI
9	Luo C, Wang Y, Chen Q, et al: Advances of paclitaxel formulations based on nanosystem delivery technology. Mini Rev Med Chem. 12:434–444. 2012. View Article : Google Scholar : PubMed/NCBI
10	Elsadek B and Kratz F: Impact of albumin on drug delivery - new applications on the horizon. J Control Release. 157:4–28. 2012. View Article : Google Scholar : PubMed/NCBI
11	Ribeiro JT, Macedo LT, Curigliano G, et al: Cytotoxic drugs for patients with breast cancer in the era of targeted treatment: back to the future? Ann Oncol. 23:547–555. 2012. View Article : Google Scholar : PubMed/NCBI
12	Ferlini C, Gallo D and Scambia G: New taxanes in development. Expert Opin Investig Drugs. 17:335–347. 2008. View Article : Google Scholar : PubMed/NCBI
13	Porche DJ: Liposomal doxorubicin (Doxil). J Assoc Nurses AIDS Care. 7:55–59. 1996. View Article : Google Scholar
14	Petrikkos GL: Lipid formulations of amphotericin B as first-line treatment of zygomycosis. Clin Microbiol Infect. 15(Suppl 5): 87–92. 2009. View Article : Google Scholar : PubMed/NCBI
15	Zhang JA, Anyarambhatla G, Ma L, et al: Development and characterization of a novel Cremophor EL free liposome-based paclitaxel (LEP-ETU) formulation. Eur J Pharm Biopharm. 59:177–187. 2005. View Article : Google Scholar : PubMed/NCBI
16	Fasol U, Frost A, Buchert M, et al: Vascular and pharmacokinetic effects of EndoTAG-1 in patients with advanced cancer and liver metastasis. Ann Oncol. 23:1030–1036. 2012. View Article : Google Scholar : PubMed/NCBI
17	Rosiello AP, Essignmann JM and Wogan GN: Rapid and accurate determination of the median lethal dose (LD50) and its error with a small computer. J Toxicol Environ Health. 3:797–809. 1977. View Article : Google Scholar : PubMed/NCBI
18	Rose WC: Taxol-based combination chemotherapy and other in vivo preclinical antitumor studies. J Natl Cancer Inst Monogr. 47–53. 1993.PubMed/NCBI
19	Wang H, Li H, Zuo M, et al: Lx2-32c, a novel taxane and its antitumor activities in vitro and in vivo. Cancer Lett. 268:89–97. 2008. View Article : Google Scholar : PubMed/NCBI
20	Szebeni J: Complement activation-related pseudoallergy: a new class of drug-induced acute immune toxicity. Toxicology. 216:106–121. 2005. View Article : Google Scholar : PubMed/NCBI
21	Karasuyama H, Tsujimura Y, Obata K and Mukai K: Role for basophils in systemic anaphylaxis. Chem Immunol Allergy. 95:85–97. 2010. View Article : Google Scholar
22	Bossi F, Fischetti F, Pellis V, et al: Platelet-activating factor and kinin-dependent vascular leakage as a novel functional activity of the soluble terminal complement complex. J Immunol. 173:6921–6927. 2004. View Article : Google Scholar
23	Cabanes A, Briggs KE, Gokhale PC, Treat JA and Rahman A: Comparative in vivo studies with paclitaxel and liposome-encapsulated paclitaxel. Int J Oncol. 12:1035–1040. 1998.PubMed/NCBI
24	Xia XJ, Guo RF, Liu YL, et al: Formulation, characterization and hypersensitivity evaluation of an intravenous emulsion loaded with a paclitaxel-cholesterol complex. Chem Pharm Bull (Tokyo). 59:321–326. 2011. View Article : Google Scholar

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Related Articles