title: Efficacies of cyclodextrin-complexed and liposome-encapsulated clarithromycin against Mycobacterium avium complex infection in human macrophages.
abstract: Cyclodextrins and liposomes have been used in recent years as drug delivery vehicles, improving the bioavailability and therapeutic efficacy of many poorly water-soluble drugs. In this study, we used two approaches to enhance the availability of the poorly water-soluble antibiotic, clarithromycin, by inclusion complex formation and by liposome-encapsulation. We examined the efficacies of these formulations against Mycobacterium avium complex (MAC) in human peripheral blood monocyte-derived macrophages. The water solubility of clarithromycin was enhanced by about 700-fold by complexation with cyclodextrin. The use of a rapid radiometric (BACTEC) method for the detection of MAC growth and susceptibility showed identical MICs against MAC for both the free and complexed drug. The anti-MAC efficacy of the cyclodextrin complex of clarithromycin in macrophages was slightly lower than the free drug, probably due to the high stability of the inclusion complex. At higher drug concentrations, Liposome-encapsulated clarithromycin was slightly more effective against intracellular MAC growth than the free drug.
authors.affiliation: Department of Microbiology, University of the Pacific, 2155 Webster Street, San Francisco, CA 94115, USA. ismail@ugr.es
authors.forename: Isam Ismail
authors.initials: II
authors.lastname: Salem
authors.forename: Nejat
authors.initials: N
authors.lastname: Düzgünes
mesh_terms: D017291:Clarithromycin / Q000737:chemistry / Q000494:pharmacology*; D003505:Cyclodextrins / Q000737:chemistry / Q000494:pharmacology*; D004339:Drug Compounding / Q000379:methods; D006801:Humans; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects* / Q000382:microbiology* / Q000502:physiology; D008826:Microbial Sensitivity Tests / Q000706:statistics & numerical data; D015269:Mycobacterium avium Complex / Q000187:drug effects* / Q000502:physiology
chemical_list: D003505:Cyclodextrins; D008081:Liposomes; D017291:Clarithromycin