Self-assembled nanoparticles of cholesterol-conjugated carboxymethyl curdlan as a novel carrier of epirubicin.
The purpose of this study was to develop nanoparticles made of cholesterol-conjugated carboxymethyl curdlan (CCMC) entrapping epirubicin (EPB) and establish their in vitro and in vivo potential. CCMC was synthesized and characterized by Fourier transform infrared spectra (FT-IR) and proton nuclear magnetic resonance spectra ((1)H 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 loading method. The physicochemical characteristics, drug loading efficiency and drug release kinetics of EPB-loaded CCMC-3.5 nanoparticles were characterized. The in vitro release profiles revealed that EPB release was sensitive to the pH as well as the drug loading contents. The cellular cytotoxicity and cellular uptake were accessed by using human cervical carcinoma (HeLa) cells. The EPB-loaded CCMC-3.5 nanoparticles were found to be more cytotoxic and have a broader distribution within the cells than the free EPB. The in vivo pharmacokinetics and biodistribution were investigated after intravenous injection in rats. Promisingly, a 4.0-fold increase in the mean residence time (MRT), a 4.31-fold increase in the half-life time and a 6.69-fold increase in the area under the curve (AUC 0-->infinity) of EPB were achieved for the EPB-loaded CCMC-3.5 self-assembled nanoparticles compared with the free EPB. The drug level was significantly increased in liver at 24 and 72 h; however, it decreased in heart at 8 and 24 h compared with the free EPB. The in vivo anti-tumor study indicated that the EPB-loaded CCMC-3.5 self-assembled nanoparticles showed greater anti-tumor efficacy than the free EPB. Taken together, the novel CCMC self-assembled nanoparticles might have potential application as anti-cancer drug carriers in a drug delivery system due to good results in vitro and in vivo.
Institute of Biomedical Engineering, Chinese Academy of Medical Sciences, Peking Union Medical College, The Key Laboratory of Biomedical Material of Tianjin, Tianjin 300192, People's Republic of China.
Lei
L
Li
Fu-ping
FP
Gao
Hong-bo
HB
Tang
Yong-gang
YG
Bai
Rui-feng
RF
Li
Xue-min
XM
Li
Ling-rong
LR
Liu
Yin-song
YS
Wang
Qi-qing
QQ
Zhang
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D015251:Epirubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000473:pathology; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D013055:Spectrophotometry, Infrared; D014018:Tissue Distribution / Q000187:drug effects; D047071:beta-Glucans / Q000737:chemistry*
D004337:Drug Carriers; D047071:beta-Glucans; C063424:carboxymethylcurdlan; D015251:Epirubicin; D002784:Cholesterol