Characterization of cisplatin cytotoxicity delivered from PLGA-systems
Daniel Moreno (a), Conchita Tros de Ilarduya (a), Eva Bandrés (b), María Buñuales (a), María Azcona (a), Jesus García-Foncillas (a), María J. Garrido (a)
(a) Department of Pharmacy and Pharmaceutical Technology, University of Navarra, Pamplona, Spain
(b) Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
Revista: European Journal of Pharmaceutics and Biopharmaceutics
Fecha: 01/03/2008Oncología Médica
Biodegradable lactic acid-glycolic acid copolymer (PLGA) formulations incorporating cisplatin have been developed to evaluate the cytotoxicity of this agent in cultured cells.
Two different W/O/W protocols were used to formulate micro- (MP) and nanoparticles (NP) under the solvent evaporation method. Although the amount of cisplatin encapsulated was higher in the MP, the efficiency of encapsulation was similar: 10.33% vs. 11.23%, for both MP and NP, respectively.
The "in-vitro" release profiles displayed a significant difference in the initial burst effect, which had a significant impact in the antiproliferative effect of cisplatin. In addition, a duality in the cell cycle distribution was found for both formulations and low doses of free cisplatin (2.5, 10 microM) in comparison with the high doses of free cisplatin. The 50 microM caused a rapid inhibition of cells growth followed by a significant loss of cells in phases G0/G1 and G2/M which correlated with an increase in the number of cells in sub-G1. However, cisplatin released from controlled formulations induced an accumulation of cells in the phase G2/M. These results led to enhance the caspase-3 activity for MP and NP.
These findings indicate that controlled release formulations of cisplatin are able to induce a more effective apoptosis than free cisplatin.
CITA DEL ARTÍCULO Eur J Pharm Biopharm. 2008 Mar;68(3):503-12
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