Otimização de nanoemulsões modificadas com transferrina como carreadores de atovaquona a erotrócitos

Abstract

Nanosystems have been proposed as new therapeutic alternatives against malaria, a disease that causes considerable social and economic losses to the affected population. The use of transferrin (TF) has been reported as a promising surface modifier for the delivery of nanostructures to. This study proposed to optimize the composition of a cationic nanoemulsion by means of a 22factorial design, aiming at the incorporation of atovaquone and the extemporaneous adsorption of TF on the surface of the emulsion droplet. Four control nanoemulsions were also prepared in order to evaluate the effect of the constituents on the formulation. So, it was possible to select the formulation with the highest zeta potential and the lowest size distribution and mean droplet size, containing 0.14% DOTAP and 0.5% polysorbate 80. The results suggested that 0.1% TF could be satisfactorily complexed to the nanoemulsion by simple mixing, confirmed by the change in droplet charge even at different pHs. The electrophoretic run confirmed that, even in the absence of positive charges (control formulation), the NE-TF interaction occurs, possibly due to additional forces, different from the electrostatic ones. Morphological analyzes also suggested the presence of protein among nanoemulsions droplets. In addition, a glycerol density gradiente centrifugation was proposed as an alternative technique for atovaquone encapsulation efficiency determination, which showed a high encapsulation capacity of the drug (> 96%), suggesting however, that part of the molecules could be localized at the interface of the droplets, as zeta potential changed in the presence of atovaquone. Finally, the study demonstrated the maintenance of the integrity (hemolytic potential lower than 10%) and functionality of the erythrocyte membrane in the presence of nanoemulsions, also indicating that the intra-erythrocyte concentration of the drug was favored by the presence of TF in the formulation.