alexa Docetaxel-albumin conjugates: preparation, in vitro evaluation and biodistribution studies.
Materials Science

Materials Science

Journal of Nanomedicine & Nanotechnology

Author(s): Esmaeili F, Dinarvand R, Ghahremani MH, Amini M, Rouhani H,

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Abstract Docetaxel (DTX) is one of the most active chemotherapeutic agents for treating metastatic breast cancer. Its aqueous solubility is very low, hence the available formulation of DTX for clinical use consists of high concentrations of tween80, which has been associated with several hypersensitivity reactions. To reduce the systemic toxicity of DTX as well as to avoid the use of tween80, in this study DTX was chemically conjugated with human serum albumin via a succinic spacer. A high-performance liquid chromatography method was developed for the determination of DTX-albumin conjugate. T47D and SKOV3 cells were used for the evaluation of the in vitro cytotoxicity of the conjugate by MTT assay. Studies were then done on balb/c mice to elucidate the tissue distribution of conjugates after intravenous administration. The albumin-conjugated formulation of DTX with the particle size of 90-110 nm showed enhanced solubility and in vivo characteristics and significantly higher cytotoxicity against tumor cells, for example, IC50 of 6.30 +/- 0.73 nM for T47D cell line compared to free DTX with IC50 of 39.4 +/- 1.75 nM. Conjugation also maintained DTX plasma level at 16.19\% up to 2 h after injection compared with 2.51\% for Taxotere, hence increasing the chance of nanoparticles uptake by tumor cells. Copyright 2009 Wiley-Liss, Inc. This article was published in J Pharm Sci and referenced in Journal of Nanomedicine & Nanotechnology

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