ABSTRACT
Encapsulation of certain antibiotics in liposomes can enhance their effect against microorganisms invading cultured cells and in animal models. We describe the incorporation of amikacin, streptomycin, ciprofloxacin, sparfloxacin, and clarithromycin in a variety of liposomes. We delineate the methods used for the evaluation of their efficacy against Mycobacterium avium-intracellulare complex (MAC) infections in macrophages and in the beige mouse model of MAC disease. We also describe the efficacy of pH-sensitive liposomes incorporating sparfloxacin or azithromycin. We summarize studies with other antibiotics, including rifampicin, rifabutin, ethambutol, isoniazid, clofazimine, and enrofloxacin, and their use against MAC, as well as other infection models, including Mycobacterium tuberculosis.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Drug Carriers , Liposomes , Mycobacterium avium-intracellulare Infection/drug therapy , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/metabolism , Cell Line , Female , Humans , Hydrogen-Ion Concentration , Liposomes/chemistry , Macrophages/cytology , Macrophages/metabolism , Macrophages/microbiology , Male , Mice , Mice, Inbred Strains , Mycobacterium avium ComplexABSTRACT
The intracellular activity of certain antiviral agents, including antisense oligonucleotides, acyclic nucleoside phosphonates, and protease inhibitors, is enhanced when they are delivered in liposome-encapsulated form. In this chapter we describe the preparation of pH-sensitive liposomes encapsulating antisense oligonucleotides, ribozymes, and acyclic nucleoside phosphonate analogues and their effects on HIV replication in macrophages. We outline the use of liposomal HIV protease inhibitors in infected macrophages. We present two methods for the covalent coupling of soluble CD4 to liposomes and show the association of these liposomes with HIV-infected cells. We also describe the synthesis of a novel antiviral agent based on cyclodextrin and its incorporation into liposomes.