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Int J Oncol. 2018 Sep;53(3):1105-1117. doi: 10.3892/ijo.2018.4449. Epub 2018 Jun 21.

Liposomal paclitaxel induces fewer hematopoietic and cardiovascular complications than bioequivalent doses of Taxol.

Author information

1
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan, R.O.C.
2
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan, R.O.C.
3
Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan, R.O.C.
4
Department of Pathology, College of Medicine, National Taiwan University, Taipei 100, Taiwan, R.O.C.

Abstract

Paclitaxel (PTX) exhibits potent antineoplastic activity against various human malignancies; however, clinical application must overcome the inherent hydrophobicity of this molecule. The commercialized Taxol formulation utilizes Cremophor EL (CrEL)/ethanol as a solvent to stabilize and dispense PTX in an aqueous solution. However, adverse CrEL‑induced hypersensitivity reactions have been reported in ~30% of recipients, and 40% of patients receiving premedication may also experience this adverse effect. Therefore, the development of a CrEL-free delivery system is crucial, in order to fully exploit the therapeutic efficacy of PTX. In the present study, a novel liposomal PTX (lipo‑PTX) formulation was optimized with regards to encapsulation rate and long‑term stability, arriving at a molar constituent ratio of soybean phosphatidylcholine:cholesterol:N-(carbonyl-methoxy-poly-ethylene glycol 2000)‑1,2‑distearoyl‑sn-glycero‑3-phosphoethanolamine, sodium salt:PTX at 95:2:1:2. Comparable doses of lipo‑PTX and Taxol were bioequivalent in terms of therapeutic efficacy in xenograft tumor models. However, the systemic side effects, including hematopoietic toxicity, acute hypersensitivity reactions and cardiac irregularities, were significantly reduced in lipo‑PTX‑treated mice compared with those infused with reference formulations of PTX. In conclusion, the present study reported that lipo‑PTX exhibited a higher therapeutic index than clinical PTX formulations.

PMID:
29956746
PMCID:
PMC6065427
DOI:
10.3892/ijo.2018.4449
[Indexed for MEDLINE]
Free PMC Article

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