Self-assembled nanoparticles of cholesterol-conjugated carboxymethyl curdlan as a novelcarrier of epirubicin

Abstract

The purpose of this study was to develop nanoparticles made of cholesterol-conjugatedcarboxymethyl curdlan (CCMC) entrapping epirubicin (EPB) and establish their invitro and in vivo potential. CCMC was synthesized and characterized by Fouriertransform infrared spectra (FT-IR) and proton nuclear magnetic resonance spectra (1H NMR). The degrees of substitution (DS) of the cholesterol moiety were 2.3, 3.5 and 6.4,respectively. EPB-loaded CCMC-3.5 nanoparticles were prepared by the remote loadingmethod. The physicochemical characteristics, drug loading efficiency and drug releasekinetics of EPB-loaded CCMC-3.5 nanoparticles were characterized. The in vitrorelease profiles revealed that EPB release was sensitive to the pH as well as thedrug loading contents. The cellular cytotoxicity and cellular uptake were accessedby using human cervical carcinoma (HeLa) cells. The EPB-loaded CCMC-3.5nanoparticles were found to be more cytotoxic and have a broader distribution within thecells than the free EPB. The in vivo pharmacokinetics and biodistribution wereinvestigated after intravenous injection in rats. Promisingly, a 4.0-fold increase inthe mean residence time (MRT), a 4.31-fold increase in the half-life time and a6.69-fold increase in the area under the curve of EPB were achieved for the EPB-loaded CCMC-3.5 self-assembled nanoparticlescompared with the free EPB. The drug level was significantly increased in liver at 24 and72 h; however, it decreased in heart at 8 and 24 h compared with the free EPB. The in vivoanti-tumor study indicated that the EPB-loaded CCMC-3.5 self-assembled nanoparticlesshowed greater anti-tumor efficacy than the free EPB. Taken together, the novelCCMC self-assembled nanoparticles might have potential application as anti-cancerdrug carriers in a drug delivery system due to good results in vitro and in vivo.