Magnetic poly ε-caprolactone nanoparticles containing Fe3O4 and gemcitabine enhance anti-tumor effect in pancreatic cancer xenograft mouse model

被引:55
作者
Gang, Jingu
Park, Seong-Bae
Hyung, Woochan
Choi, Eric H.
Wen, Jing
Kim, Han-Soo
Shul, Young-Gun
Haam, Seungjoo
Song, Si Young
机构
[1] Yonsei Univ, Coll Med, Dept Internal Med, Inst Gastroenterol, Seoul 120752, South Korea
[2] Yonsei Univ, Coll Engn, Dept Chem Engn, Seoul, South Korea
[3] Yonsei Univ, Bioprod Res Ctr, Seoul, South Korea
[4] Yonsei Univ, Coll Med, Brain Korea 21 Project Med Sci, Seoul, South Korea
关键词
magnetic nanoparticles; drug targeting; pancreatic cancer; gemcitabine; in vivo;
D O I
10.1080/10611860701453901
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
We prepared magnetic (Fe3O4) poly F-caprolactone (PCL) nanoparticles (mean diameter 164 +/- 3nm) containing an anticancer drug (gemcitabine) using emulsion-diffusion method in order to develop more efficient drug delivery for cancer treatment. Nanoparticles were smooth, well individualized and homogeneous in size. The values of magnetizations for the magnetic PCL nanoparticles were observed around 10.2 emu/g at 2000 Oe magnetic field intensity and showed superparamagnetic property. In case of the drug, the drug loading contents was 18.6% and entrapment efficiency was 52.2%. The anti-tumor effects caused by these particles were examined using nude mice bearing subcutaneous human pancreatic adenocarcinoma cells (HPAC) in vivo. We divided that these mice were randomly assigned to one of five treatment groups for experimental contrast. The antitumor effect was showed with 15-fold higher dose when compared to free gemcitabine. From the result, the magnetic PCL nanoparticles may provide a therapeutic benefit by delivering drugs efficiently to magnetically targeted tumor tissues, thus achieving safe and successful anti-tumor effects with low toxicity.
引用
收藏
页码:445 / 453
页数:9
相关论文
共 37 条
[21]   Paclitaxel loaded poly(L-lactic acid) microspheres for the prevention of intraperitoneal carcinomatosis after a surgical repair and tumor cell spill [J].
Liggins, RT ;
D'Amours, S ;
Demetrick, JS ;
Machan, LS ;
Burt, HM .
BIOMATERIALS, 2000, 21 (19) :1959-1969
[22]  
Lubbe AS, 1996, CANCER RES, V56, P4694
[23]  
Lubbe AS, 1996, CANCER RES, V56, P4686
[24]   Clinical applications of magnetic drug targeting [J].
Lübbe, AS ;
Alexiou, C ;
Bergemann, C .
JOURNAL OF SURGICAL RESEARCH, 2001, 95 (02) :200-206
[25]   Tumour targeted delivery of encapsulated dextran-doxorubicin conjugate using chitosan nanoparticles as carrier [J].
Mitra, S ;
Gaur, U ;
Ghosh, PC ;
Maitra, AN .
JOURNAL OF CONTROLLED RELEASE, 2001, 74 (1-3) :317-323
[26]   Advancing the field of drug delivery: Taking aim at cancer [J].
Moses, MA ;
Brem, H ;
Langer, R .
CANCER CELL, 2003, 4 (05) :337-341
[27]   Preparation of poly(DL-lactide-co-glycolide) nanoparticles by modified spontaneous emulsification solvent diffusion method [J].
Murakami, H ;
Kobayashi, M ;
Takeuchi, H ;
Kawashima, Y .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1999, 187 (02) :143-152
[28]   Further application of a modified spontaneous emulsification solvent diffusion method to various types of PLGA and PLA polymers for preparation of nanoparticles [J].
Murakami, H ;
Kobayashi, M ;
Takeuchi, H ;
Kawashima, Y .
POWDER TECHNOLOGY, 2000, 107 (1-2) :137-143
[29]   Lymphatic targeting with nanoparticulate system [J].
Nishioka, Y ;
Yoshino, H .
ADVANCED DRUG DELIVERY REVIEWS, 2001, 47 (01) :55-64
[30]   The preparation and evaluation of poly(ε-caprolactone) microparticles containing both a lipophilic and a hydrophilic drug [J].
Pérez, MH ;
Zinutti, C ;
Lamprecht, A ;
Ubrich, N ;
Astier, A ;
Hoffman, M ;
Bodmeier, R ;
Maincent, P .
JOURNAL OF CONTROLLED RELEASE, 2000, 65 (03) :429-438