Targeted Delivery of Cabazitaxel by Conjugation to Albumin-Peg-Folate Nanoparticles Using a Cysteine-Acrylate Linker and Simple Synthesis Conditions Publisher Pubmed



Khoeeniha MK¹ ; Esfandyarimanesh M² ; Behrouz H¹ ; Amini M³ ; Varnamkhast BS² ; Atyabi F^{1, 2} ; Dinarvand R^{1, 2}
Source: Current Drug Delivery Published:2017

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. © 2017 Bentham Science Publishers.