Targeted Delivery of Cabazitaxel by Conjugation to Albumin-PEG-folate Nanoparticles Using a Cysteine-acrylate Linker and Simple Synthesis Conditions

Author(s): Mohammad Kazem Khoeeniha, Mehdi Esfandyari-Manesh, Hossein Behrouz, Mohsen Amini, Behrang Shiri Varnamkhasti, Fatemeh Atyabi, Rassoul Dinarvand*

Journal Name: Current Drug Delivery

Volume 14 , Issue 8 , 2017

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Graphical Abstract:


Background: Cabazitaxel (CBZ) is a new taxane approved by FDA for treatment of castration- resistant prostate cancer not responding to docetaxel. However, CBZ is not a suitable substrate for p-glycoprotein 60, an efflux pump which transports anticancer drugs out of malignant cells and is therefore a promising drug for treatment of multidrug resistant tumors. Similar to other taxanes, the presence of Tween 80 in the CBZ formulation shows that it is insoluble in water.

Methods: In order to increase the solubility and circulation time of this drug, CBZ-human serum albumin (HSA) conjugate was synthesized. The designed linker was composed of methacrylic acid and N-acetyl cysteine to increase the solubility of CBZ and to increase the efficiency of conjugation. Targeting was performed by poly(ethylene glycol)-folic acid amide bound formation with carboxyl groups of HSA during in the step of nanoparticle formation. Cytotoxicity of nanoparticles was evaluated in vitro on HT-29, as a folate negative cell line, and MDA-MB-231, as a folate positive cell line.

Results: H-NMR, Gel Permeation Chromatography, High Pressure Liquid Chromatography and UV spectrophotometry analysis confirmed the composition of conjugates. The resulting nanoparticles had a spherical shape, narrow size distribution and mean diameter of 138 nm. The efficiency of conjugation was 41.6 %. The IC50 of CBZ in targeted nanoparticles was 10.1 and 17.4% lower than that of the free CBZ for HT-29 and MDA-MB-231 cells, respectively.

Conclusion: This designed drug delivery system was more water-soluble and had enhanced in vitro characteristics and higher cytotoxic activity on cancer cells.

Keywords: Cabazitaxel, conjugate, human serum albumin, nanoparticle, targeting, gel permeation chromatography.

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Article Details

Year: 2017
Published on: 22 November, 2016
Page: [1120 - 1129]
Pages: 10
DOI: 10.2174/1567201814666161122150302
Price: $65

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