Increasing the selectivity of amikacin in rat peritoneal macrophages using carrier erythrocytes

The selectivity of amikacin in macrophages in vitro and its biodistribution in peritoneal macrophages and other tissues were studied in rats using carrier erythrocytes. Amikacin-loaded erythrocytes were prepared using a hypotonic dialysis method. The in vitro uptake of amikacin by peritoneal macrophages was studied using cell monolayers. The in vivo uptake by macrophages and the tissue distribution of amikacin were studied in two groups of rats that received either amikacin in saline solution, or amikacin-loaded erythrocytes. Pharmacokinetic analyses were performed using model-independent methods. The administration of the antibiotic using carrier erythrocytes elicited a higher accumulation in macrophages, both in vitro and in vivo. The tissue pharmacokinetics of amikacin in vivo using carrier erythrocytes revealed an accumulation of the antibiotic in specific tissues such as the liver and spleen. Minor changes in the pharmacokinetics were observed in organs and tissues such as renal cortex and medulla. According to the partition coefficients obtained, the relative uptake of amikacin when carrier erythrocytes were used was: spleen > peritoneal macrophages > liver > lung > renal cortex > renal medulla. Loaded erythrocytes can be seen to be potentially useful for the delivery of aminoglycoside antibiotics in macrophages. (C) 2009 Elsevier B.V. All rights reserved.