NK105, a paclitaxel-incorporating micellar nanoparticle formulation, can extend in vivo antitumour activity and reduce the neurotoxicity of paclitaxel
| Autor: | Tadao Kakizoe, Minoru Suzuki, Tetsuya Hamaguchi, M. Yokoyama, I Nakamura, Kazunori Kataoka, K Shimizu, R Goda, I Nakatomi, Yasuhiro Matsumura |
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| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
Paclitaxel Chemistry Pharmaceutical Transplantation Heterologous Pharmacology Nervous System DDS Mice chemistry.chemical_compound Pharmacokinetics In vivo Animals Humans Medicine business.industry Neurotoxicity Area under the curve EPR effect NK105 medicine.disease Antineoplastic Agents Phytogenic polymer micelles Nanostructures Transplantation Oncology chemistry Area Under Curve Pharmacodynamics Colonic Neoplasms Cancer cell Translational Therapeutics business |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/sj.bjc.6602479 |
| Popis: | Paclitaxel (PTX) is one of the most effective anticancer agents. In clinical practice, however, high incidences of adverse reactions of the drug, for example, neurotoxicity, myelosuppression, and allergic reactions, have been reported. NK105, a micellar nanoparticle formulation, was developed to overcome these problems and to enhance the antitumour activity of PTX. Via the self-association process, PTX was incorporated into the inner core of the micelle system by physical entrapment through hydrophobic interactions between the drug and the well-designed block copolymers for PTX. NK105 was compared with free PTX with respect to their in vitro cytotoxicity, in vivo antitumour activity, pharmacokinetics, pharmacodynamics, and neurotoxicity. Consequently, the plasma area under the curve (AUC) values were approximately 90-fold higher for NK105 than for free PTX because the leakage of PTX from normal blood vessels was minimal and its capture by the reticuloendothelial system minimised. Thus, the tumour AUC value was 25-fold higher for NK105 than for free PTX. NK105 showed significantly potent antitumour activity on a human colorectal cancer cell line HT-29 xenograft as compared with PTX (P |
| Databáze: | OpenAIRE |
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