Characterization and in vitro cytotoxicity of doxorubicin-loaded γ-polyglutamic acid-chitosan composite nanoparticles

被引:25
|
作者
Hellmers, Frank [1 ,2 ]
Ferguson, Peter [3 ,4 ,5 ]
Koropatnick, James [3 ,4 ,5 ]
Krull, Rainer [2 ]
Margaritis, Argyrios [1 ]
机构
[1] Univ Western Ontario, Dept Chem & Biochem Engn, London, ON N6A 5B9, Canada
[2] Tech Univ Carolo Wilhelmina Braunschweig, Inst Biochem Engn, D-38106 Braunschweig, Germany
[3] Canc Res Lab Program, London Reg Canc Program, London, ON N6A 4L6, Canada
[4] Lawson Hlth Res Inst, London, ON N6A 4L6, Canada
[5] Univ Western Ontario, Dept Oncol, London, ON N6A 5B9, Canada
基金
加拿大自然科学与工程研究理事会; 加拿大健康研究院;
关键词
Chitosan; Controlled release; Cytotoxicity; Doxorubicin; gamma-polyglutamic acid; Nanoparticles; DRUG-DELIVERY; PARTICLE-SIZE; SOLID TUMOR; PERMEABILITY; RELEASE; STORAGE; PH;
D O I
10.1016/j.bej.2013.03.019
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
In this study, gamma-polyglutamic acid (gamma-PGA) and chitosan (CS) nanoparticles were characterized as a carrier for the anti-cancer drug doxorubicin (DOX). Using ionic complexation between the positively charged DOX and the negatively charged polyelectrolyte gamma-PGA, DOX:gamma-PGA complexes were produced with an efficiency of approximately 99%. SEM micrographs demonstrated that the complexation of gamma-PGA and DOX alone does not lead to the formation of nanoparticles and that the addition of a third component, chitosan, is required. Drug-loaded DOX:gamma-PGA:CS nanoparticles were produced with particle sizes ranging from similar to 150 to similar to 630 nm. The stability of the DOX:gamma-PGA:CS nanoparticles was examined by suspending the nanoparticles in different kinds of aqueous media. For the first time, in vitro studies with DOX-loaded nanoparticles demonstrated the cytotoxicity of the nanoparticles against a human oral squamous cell carcinoma cell line (HN-5a). Non-drug-loaded gamma-PGA:CS nanoparticles did not display cytotoxic effects. It was shown that the encapsulated or surface-bound DOX did not lose its bioactivity and the prepared drug-loaded particles exhibited a considerable anti-proliferative activity against the human cancer cell line. (C) 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码:72 / 78
页数:7
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