RESUMEN
Complexation of antitumor drug, doxorubicin (DOX), with poly(acrylic acid) (PAA) in buffer solutions was examined. The DOX-to-PAA binding was governed by electrostatic and stacking interactions resulting in a complex of characteristic composition with a PAA/DOX = 1.6 molar ratio. Sizes of the complex particles were found to lie in 600-900-nm range. However, the particles were able to interact with small neutral egg yolk lecithin liposomes (80-100 nm in diameter), a ternary DOX/PAA/liposome complex being formed. The observations and conclusions we made may be useful for interpreting biological effects of polymer-based bioactive constructs.
Asunto(s)
Resinas Acrílicas/química , Doxorrubicina/química , Liposomas/química , Yema de Huevo/química , Tamaño de la Partícula , Fosfatidilcolinas/química , Electricidad Estática , Propiedades de SuperficieRESUMEN
A model, based on fluorescence data, is developed for the poly(acrylic acid)-assisted transport of doxorubicin, a cationic antitumor drug, through a bilayer membrane. Accordingly, the doxorubicin binds to the poly(acrylic acid) via electrostatic polymer-drug interactions plus drug-drug stacking within the complex. This complex associates with neutral egg lecithin vesicles by means of hydrophobic attraction between the doxorubicin and the vesicle bilayers. In the process, the doxorubicin "destacks", providing a fluorescence change that can be monitored. Finally, the doxorubicin enters the vesicle interior which has been imparted with an acidic pH to protonate the doxorubicin and thus, in a second stage, yield an additional fluorescence change that can also be detected. A portion of the poly(acrylic acid), now devoid of doxorubicin, then leaves the outer vesicle surface and enters to external solution.
