Nanoestructuras basadas en copolímero en bloque anfifílico y miltefosina para el tratamiento de cáncer

VALENZUELA-OSES, JOHANNA; GARCÍA, MÓNICA C; LOURENÇO, FELIPE; RANGEL YAGUI, CARLOTA

Congreso; XXVIII Congreso Peruano de Química; 2017

Miltefosine is an alkylphosphocholine drug with antineoplastic activity but high hemolytic potential1. In this work, we encapsulated miltefosine into polymeric micelles of the copolymer Pluronic F127. A central composite design was applied to optimize the formulation parameters and to study the effects of hydration temperature, stirring speed and stirring time on the hydrodynamic diameter (Dh) and polydispersity index (PI) (response variables)2. Second order models were obtained to adequately describe the influence of the independent variables on the selected response. Analysis of variance showed that temperature had significant effect (p<0.05) on the polydispersity index. The optimum level of Dh and PI predicted by the model and conformed experimentally were 29.09 ± 0.168 nm and 0.105 ± 0.005 respectively corresponding to hydration temperature of 23 oC, stirring speed of 480 RPM and 20 min of stirring time. Differential scanning calorimetry (DSC) and Thermogravimetric (TG) analyses confirmed that the drug was molecularly dispersed within the micelles. Physical stability of the lyophilized optimal formulation after 3 months storage at 4°C showed high stability with low polydispersity index (0.189). In vitro cytotoxicity against HeLa and H358 cells demonstrated that the cytotoxic effect of Pluronic F127-miltefosine micelles was similar to the one of free miltefosine. Additionally, drug incorporation into polymeric micelles significantly decreased hemolytic effect. Pluronic F127-miltefosine micelles with 80 µM of miltefosine were found to be no hemolytic in comparison to a hemolytic potential of 30 % for the same concentration of free drug. Our results suggest that by lowering hemolytic potential, Pluronic F127-miltefosine micelles represent a promising strategy to broader the use of this drug as well as of other alkylphosphocholines, in cancer therapy.