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.