Experimental investigation of pharmacokinetic properties and the accumulation of zinc when administrated nanoform of zinc hydroxide in a comparative aspect with zinc sulfate

Аннотация

Pharmacological correction of the imbalance of zinc is important for a comprehensive treatment of microelementoses human. Existing zinc preparations limited in their application, so as active ingredients used oxide and zinc sulfate. Nowadays, with the development of physical and chemical methods of dispersion increases the amount of information about more effective action nanoforms zinc compounds. Via sol-gel method, nanoparticles (2-3 nm) of zinc hydroxide were obtained, which were measured by small angle X-ray scattering. The purpose of a preliminary assessment of the biological effect, a comparative study of nanoparticles using test cultures of bakery yeast, the results of which determined the level of inhibition, which was higher than 90%, compared with the figure for the zinc sulfate and the above 145% more compared to the zinc oxide. Investigation was performed on the pharmacokinetic characteristics of the 40 rabbits-males in comparison with that using zinc sulfate, in an enteral or intravenous administration at three dose levels: 10, 50 and 100 mg/kg. The time to reach maximum concentration of Zn2 + in enteral administration of nanoform was 4 hours, which is faster than that of zinc sulfate - 6 hours. The total clearance of nanoparticles increases with dose increases, amounting to 9.60±0.38, 13.96±0.24, 15.55±0.12 ml/h, half-life is not a statistically significant change. High parameters determined for the absolute bioavailability of zinc in enteral administration of zinc hydroxide nanoparticles - 30.33 ± 3.16, 44.39 ± 4.52 and 42.47 ± 3.66%, respectively, for doses of 10, 50 and 100 mg/kg. The pharmacokinetic properties when administered nanoforms zinc hydroxide and zinc sulfate soluble have no significant difference (at 10 and 50 mg/kg), which, however, are shown at a dose of 100 mg/kg. Determined a more rapid time of onset of maximum concentration for nanoforms, in comparison with zinc sulfate, and high parameters absolute bioavailability for zinc in enteral introduction of nanoparticles of zinc hydroxide: - 30.33±3.16, 44.39±4.52 and 42.47±3.66%, respectively, with a dosage: 10, 50 and 100 mg/kg. The pharmacokinetic properties when administered nanoform of zinc hydroxide and soluble zinc sulfate have no significant difference (at 10 and 50 mg/kg), which, however, have difference at 100 mg/kg. Investigation accumulation dynamics was conducted on 90 rats-males Wistar under enteral administration in a dosage of 100 mg/kg, using as comparison compound, zinc sulfate. Significantly was selected (p <0.05) the maximum level of accumulation of zinc in erythrocyte mass with the introduction of nanoforms of zinc hydroxide. Also significantly was selected (p<0.05) the lowest level of accumulation of zinc in liver tissues, compared with those groups which were administered zinc sulfate and zinc hydroxide.