Journal
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Volume 70, Issue 3, Pages 726-734Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejpb.2008.06.016
Keywords
Nanoparticles; Drug delivery; Cisplatin; Antitumor; PET/CT
Categories
Funding
- National Natural Science Foundation of China [30670958]
- Jiangsu Province Key Medical Cent Foundation
- Scientific and Technological Innovation Plan Fund of Postgraduate from Jiangsu Province
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cis-Dichlorodiamminoplatinum (II) (cisplatin) has demonstrated extraordinary activities against a variety of solid tumors. However, the clinical efficacy is contrasted by its toxicity profile. To reduce the toxicity and enhance the circulation time of cisplatin, core-shell structure nanoparticles were prepared from block copolymer of methoxy poly(ethylene glycol)-polycaprolactone (mPEG-PCL). Cisplatin was incorporated into the nanoparticles with high encapsulation efficiency more than 75%. Controlled release of cisplatin was observed in a sustained manner. In vitro cytotoxicity studies proved the efficacy of cisplatin-loaded nanoparticles against BGC823 and H-22 cells in a dose and time-dependent manner. Furthermore, intratumoral administration was applied to improve the tumor-targeted delivery in the in vivo evaluation. Compared with free cisplatin, cisplatin-loaded nanoparticles exhibited superior antitumor effect by delaying tumor growth when delivered intratumorally, while no significant improvement was observed when they were administrated intraperitoneally. Positron emission tomography/computed tomography (PET/CT) imaging was utilized for the first time to detect the declined F-18-labeled 2-fluoro-2-deoxy-D-glucose (F-18-FDG) uptake of the tumor in mice receiving cisplatin-loaded nanoparticles intratumorally. These results suggest that polymeric nanoparticles with core-shell structures are promising for further studies as drug delivery carriers, and intratumoral delivery of drug-loaded nanoparticles could be a probable clinically useful therapeutic regimen. (C) 2008 Elsevier B.V. All rights reserved.
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