Development and characterization of nanoparticles containing nanoencapsulated vanadium compounds for the treatment of diabetic retinopathy in the State of Pernambuco
Diabetes, zebrafish, policaprolactone, metformin, sodium metavanadate.
This work proposed the development of polycaprolactone (PCL) and poloxamer 188 nanoparticles containing an association of metformin and nanoencapsulated sodium metavanadate as an alternative for the treatment of a zebrafish (Danio rerio) model with conditions similar to diabetes, using an incubator with photoperiod and temperature controlled to develop the animals. The incubator was developed and it was found that the stages of embryonic development of the zebrafish were not affected, indicating the possibility for toxicological tests with the model. The nanoparticles were produced using an organic phase, containing the polymer and solvents, and an aqueous phase, containing the surfactant and antidiabetic drugs, in a 1:2 ratio, under magnetic stirring. The formulations had an average size that varied between ≈ 200 nm, polydispersity index of ≈ 0.1 and zeta potential > -10 mV. For toxicological evaluation, zebrafish embryos were exposed to different concentrations (1, 5 and 10 mL) of PCL and poloxamer 188 nanoparticles containing nanoencapsulated metformin and metavanadate and evaluated for sublethal and lethal effects. The typical sublethal effects observed (p < 0.05) were pericardium and yolk sac edema and spinal deformation and the lethal effects were attributed to coagulation and absence of heartbeat, at a concentration of 1 mL no sublethal or lethality was observed (p > 0.05). After determining a safe concentration, zebrafish embryos, eleuthero-embryos and larvae were exposed to D-glucose in order to simulate diabetes-inducing conditions and treated with PCL nanoparticles. The nanoparticles were produced using the preformed polymer deposition technique and their physicochemical characteristics were analyzed in terms of the concentrations of the chemical compounds used. Zebrafish embryos, eleuthero-embryos and larvae were evaluated for sublethal and lethal effects and optomotor response. As for the physicochemical characteristics of the nanoparticles, the mean size (p < 0.05) was influenced by the concentrations of PCL, metformin and sodium metavanadate, whereas the PDI (p < 0.05) was influenced by the concentrations of PCL and metformin. As for zebrafish embryos and eleuthero-embryos, no sublethality or lethality was observed in the groups exposed without the addition of glucose. In the exposed groups with added glucose, the observed sublethal effects (p < 0.05) were
general growth retardation at 1 day post-fertilization (embryo) and pericardial edema at 3 day post-fertilization (eleuthero-embryo). In the group treated with PCL nanoparticles and poloxamer 188 with the combination of metformin and nanoencapsulated sodium metavanadate, sublethal pericardial edema (p > 0.05) was not observed, indicating a protective character of nanoparticles containing antidiabetic drugs, which may provide an alternative therapy for the treatment of diabetes.