Staphylococci surviving intracellularly in phagocytes from patients suffering from chronic granulomatous disease are killed in vitro by antibiotics encapsulated in liposomes.
Granulocytes and monocytes/macrophages from patients suffering from chronic granulomatous disease (CGD) are ineffective in killing specific kinds of phagocytized bacteria, e.g., Staphylococcus aureus, due to decreased or lacking ability to produce reactive oxygen intermediates. Commonly used antibiotics like flucloxacillin are of limited therapeutic value, because the staphylococci are protected against their action in the interior of phagocytes. However, encapsulation of flucloxacillin into liposomes could enable its entrance into the interior of neutrophils from two CGD patients to kill phagocytized bacteria there. The effect of rifampicin against intracellular staphylococci could be similarly enhanced by liposome encapsulation. Dose-response relations and kinetics of killing of intracellular bacteria by antibiotics in the free and encapsulated form were studied under different conditions using J 774 mouse macrophages, because phagocytes from CGD patients are not available in great amounts. Preincubation of phagocytes with either antibiotic in liposomes subsequently endowed the cells with a strongly enhanced ability to kill phagocytized bacteria. Our data show that a drug which normally will not reach a phagosome can be delivered to this intracellular compartment by a liposome. A possible clinical use is discussed.
Fraunhofer-Institute for Toxicology, Department of Immunobiology, Hannover, Federal Republic of Germany.
J
J
Roesler
S
S
Hockertz
B
B
Vogt
M L
ML
Lohmann-Matthes
D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D004337:Drug Carriers; D005436:Floxacillin / Q000008:administration & dosage; D006105:Granulomatous Disease, Chronic / Q000276:immunology*; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage; D009504:Neutrophils / Q000276:immunology; D010586:Phagocytes / Q000276:immunology*; D010587:Phagocytosis; D012293:Rifampin / Q000008:administration & dosage; D013210:Staphylococcus / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D008081:Liposomes; D005436:Floxacillin; D012293:Rifampin