Journal
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Volume 74, Issue 2, Pages 265-274Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejpb.2009.10.005
Keywords
Cisplatin; PLGA nanoparticles; Antiproliferative effect in vitro; Apoptosis; Antitumor efficacy in vivo
Categories
Funding
- Spanish Government [PCT-090100-2007-27]
- University of Navarra (FUN)
- Government of Navarra
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Biodegradable poly (lactic-co-glycolic) acid (PLGA) nanoparticles incorporating cisplatin have been developed to evaluate its in vivo efficacy in tumor-bearing mice. In vitro Study proved two mechanisms of action for cisplatin depending on the dose and the rate at which this dose is delivered. In vivo study, 5 mg/kg of cisplatin nanoparticles administered to mice, exhibited a tumour inhibition similar to free cisplatin, although the area under cisplatin concentration-time Curve between 0 and 21 days (AUC(0-21)) had lower Value for the formulation than for drug solution (P < 0.05). This result was associated with a higher activation of apoptosis in tumor, mediated by caspase-3, after nanoparticles administration. Toxicity measured as the change in body weight, and blood urea nitrogen (BUN) plasma levels showed that cisplatin nanoparticles treatment did not induce significant changes in both parameters compared to control, while for free drug, a statistical (P < 0.01) increase was observed. In addition, a good correlation was found between time profiles of tumor volume and vascular endothelial growth factor (VEGF) plasma levels, suggesting that its expression could help to follow the efficacy of the treatment. Therefore, the PLGA nanoparticles seem to provide a promising carrier for cisplatin administration avoiding its side effects without a reduction of the efficacy, which was consistent with a higher activation of apoptosis than free drug. (C) 2009 Elsevier B.V. All rights reserved.
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