title: Therapeutic efficacy of liposomal rifabutin in a Mycobacterium avium model of infection.
abstract: Liposomal formulations of rifabutin were developed, and the effects of some parameters on the incorporation efficiency were studied. The antimycobacterial activity of rifabutin incorporated into liposomes prepared with phosphatidylcholine and phosphatidylserine (molar ratio, 7:3) was evaluated in a murine model of infection with a virulent Mycobacterium avium strain (strain P1581) and was compared with that of free rifabutin. The influences of the size of the liposomal rifabutin formulation, the administered doses, and the treatment schedules on the evolution of infection were studied. Two types of treatment schedules were assayed: therapeutic and prophylactic. The therapeutic treatment started 2 weeks after infection, while the prophylactic treatment began 1 day before the experimental infection with mycobacteria. Incorporation of rifabutin in liposomes resulted in a significant enhancement of activity against M. avium infection compared to that of rifabutin in the free form in both schedules. These results demonstrate that liposomal formulations of antibiotics such as rifabutin may be effective for the treatment or prophylaxis of infectious diseases.
authors.affiliation: INETI, Department of Biotechnology, Unidade Novas Formas de Agentes Bioactivos, Lisbon, Portugal. manuela.gaspar@ibqta.ineti.pt
authors.forename: M M
authors.initials: MM
authors.lastname: Gaspar
authors.forename: S
authors.initials: S
authors.lastname: Neves
authors.forename: F
authors.initials: F
authors.lastname: Portaels
authors.forename: J
authors.initials: J
authors.lastname: Pedrosa
authors.forename: M T
authors.initials: MT
authors.lastname: Silva
authors.forename: M E
authors.initials: ME
authors.lastname: Cruz
mesh_terms: D000818:Animals; D019072:Antibiotic Prophylaxis; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical; D002784:Cholesterol / Q000737:chemistry; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004337:Drug Carriers; D016503:Drug Delivery Systems; D008081:Liposomes / Q000737:chemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009162:Mycobacterium avium / Q000187:drug effects; D017828:Rifabutin / Q000008:administration & dosage / Q000627:therapeutic use*; D014376:Tuberculosis / Q000188:drug therapy* / Q000517:prevention & control
chemical_list: D000904:Antibiotics, Antitubercular; D004337:Drug Carriers; D008081:Liposomes; D017828:Rifabutin; D002784:Cholesterol