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

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.

journal_name

Curr Drug Deliv

journal_title

Current drug delivery

authors

Khoeeniha MK,Esfandyari-Manesh M,Behrouz H,Amini M,Varnamkhasti BS,Atyabi F,Dinarvand R

doi

10.2174/1567201814666161122150302

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

1120-1129

issue

8

eissn

1567-2018

issn

1875-5704

pii

CDD-EPUB-79881

journal_volume

14

pub_type

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