Acta Pharmacologica Sinica (2009) 30: 1337–1343; doi: 10.1038/aps.2009.125

Acta Pharmacologica Sinica (2009) 30: 1337–1343; doi: 10.1038/aps.2009.125

Original Article

Preparation of albumin nanospheres loaded with gemcitabine and their cytotoxicity against BXPC-3 cells in vitro

Jin-ming LI^{1, 3, #}, Wei CHEN^{2, #}, Hao WANG², Chen JIN¹, Xian-jun YU^{1, *}, Wei-yue LU², Long CUI³, De-liang FU¹, Quan-xing NI¹, Hui-min HOU^{2, *}

¹Pancreatic Disease Institute, Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China; ²National Pharmaceutical Engineering Research Center, Shanghai Institute of Pharmaceutical Industry, Shanghai 201203, China; ³Department of Colorectal & Anal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China

Aim: To optimize formulation methods for loading gemcitabine (GEM), the main drug against pancreatic cancer, into albumin nanoparticles for extended blood circulation and improved efficacy.

Methods: GEM was loaded into two sizes of disolvation-crosslinked bovine serum albumin nanoparticles, with a mean diameter of 109.7 nm and 405.6 nm, respectively, by co-precipitation (the direct method) and follow-up adsorption (the indirect method). The antitumor activities of the two nanoparticulate formulations, were evaluated according to their anti-proliferative effects on the human pancreatic cell line BXPC-3, which were assessed using the MTT assay.

Results: The two nanoparticulate formulations, created by direct co-precipitation and indirect adsorption, possessed smooth surfaces and high drug loading efficiencies, 83% and 93% at 11% and 13% drug loading, respectively. The two formulations released GEM for 8 and 12 h, respectively, and significantly improved anti-BXPC-3 proliferation effects, as compared with the GEM solution and the drug-free albumin particles.

Conclusion: Co-precipitating and adsorbing GEM into albumin particles resulted in sustained-release nanoparticulate formulations with improved antitumor cytotoxicity. This result suggests that this is a useful formulation strategy for improving the antitumor efficacy of GEM.

Keywords: gemcitabine; serum albumin; nanoparticles; pancreatic cancer

This work was supported by the Science and Technology Commission of Shanghai Municipality (No 08431902500) and the Shanghai Municipal Economic Commission (No 06-23, 07ZH-028).

^#These two authors contributed equally to the manuscript.
* To whom correspondence should be addressed.
Emal yuxianjun88@hotmail.com; wanghao99@hotmail.com
Received 2009-05-15 Accepted 2009-07-14

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