title: Characterization of cisplatin cytotoxicity delivered from PLGA-systems.
abstract: 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.
authors: Department of Pharmacy and Pharmaceutical Technology, University of Navarra, Pamplona, Spain.
authors: Daniel
authors: D
authors: Moreno
authors: Conchita Tros
authors: CT
authors: de Ilarduya
authors: Eva
authors: E
authors: Bandrés
authors: María
authors: M
authors: Buñuales
authors: María
authors: M
authors: Azcona
authors: Jesús
authors: J
authors: García-Foncillas
authors: María J
authors: MJ
authors: Garrido
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D019344:Lactic Acid / Q000008:administration & dosage*; D053758:Nanoparticles; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats
chemical_list: D003692:Delayed-Action Preparations; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D053148:Caspase 3; D002945:Cisplatin