The mechanism of enhanced intraphagocytic killing of bacteria by liposomes containing antibiotics.
Liposomes containing aminoglycosides have been shown to enhance the killing of Brucella abortus and Staphylococcus aureus inside bovine phagocytic cells. This study examined the mechanism by which liposomes containing aminoglycoside enhance the intracellular killing of bacteria. Liposomes with entrapped aminoglycoside were found to significantly enhance the intraphagocytic killing of bacteria in bovine phagocytic cells (in vitro) when compared to free drug. Liposomes with entrapped aminoglycoside were also found to deliver significantly higher levels of aminoglycoside into phagocytic cells when compared to free drug (gentamicin) or free drug and liposomes without entrapped antibiotic. Antibiotic delivered to adherent phagocytic cells could be detected 3 days after treatment of the cells with liposomes containing aminoglycoside. No antibiotic could be detected in the supernatants of phagocytic cell cultures 3 days after treatment with liposomes containing antibiotic was only observed when the intraphagocytic bacteria were sensitive to the antibiotic entrapped in the liposomes. The rate of phagocytosis of S. aureus by cells treated with cationic liposomes (no entrapped antibiotic) did not differ from the rate of phagocytosis of control cells not treated with cationic liposomes. This study shows that the enhanced intraphagocytic killing of bacteria in bovine phagocytic cells occurs by direct delivery of entrapped antibiotic into the phagocytic cell by the liposome delivery vehicle and not by nonspecific enhancement of phagocytic cell function. Liposomes containing aminoglycoside appear to have no toxic effects on phagocytic cell function or viability in vitro.
Dees
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Department of Microbiology, School of Veterinary Medicine, Auburn University, AL 36849.
Schultz
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D000704:Analysis of Variance; D000818:Animals; D002417:Cattle; D004337:Drug Carriers; D005839:Gentamicins / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008081:Liposomes / Q000633:toxicity; D010586:Phagocytes / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects*
D004337:Drug Carriers; D005839:Gentamicins; D008081:Liposomes