Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Levofloxacin , Obesity, Morbid/complications , Ofloxacin/administration & dosage , Ofloxacin/pharmacokinetics , Pneumococcal Infections/drug therapy , Body Weight , Humans , Infusions, Intravenous , Middle AgedABSTRACT
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.
Subject(s)
Amikacin/administration & dosage , Amikacin/pharmacokinetics , Drug Carriers/administration & dosage , Erythrocytes , Macrophages, Peritoneal/metabolism , Animals , Drug Carriers/pharmacokinetics , Erythrocytes/metabolism , Macrophages, Peritoneal/drug effects , Male , Rats , Rats, Wistar , Tissue Distribution/drug effects , Tissue Distribution/physiologyABSTRACT
Many infectious diseases are caused by facultative organisms that are able to survive in phagocytic cells. The intracellular location of these microorganisms protects them from the host defence systems and from some antibiotics with poor penetration into phagocytic cells. One strategy used to improve the penetration of antibiotics into phagocytic cells is the use of carrier systems that deliver these drugs directly to the target cell. Delivery systems such as liposomes, micro/nanoparticles, lipid systems, conjugates, and biological carriers such as erythrocyte ghosts may contribute to increasing the therapeutic efficacy of antibiotics and antifungal agents in the treatment of infections caused by intracellular microorganisms. The main objective of this review is to analyze recent advances and current perspectives in the use of antibiotic delivery systems in the treatment of intracellular infections such as mycobacterial infections, brucellosis, salmonellosis, listeriosis, fungal infections, visceral leishmaniasis, and HIV.