title: In vitrouptake and antimycobacterial activity of liposomal usnic acid formulation.
abstract: The cellular uptake and antimycobacterial activity of usnic acid (UA) and usnic acid-loaded liposomes (UA-LIPOs) were assessed on J774 macrophages. The minimal inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC) of UA and UA-LIPO against Mycobacterium tuberculosis were determined. Concentrations required to inhibit 50% of cell proliferation (IC(50)) were 22.5 (+/-0.60) and 12.5 (+/-0.26) microg/ml, for UA and UA-LIPO, respectively. The MICs of UA and UA-LIPO were 6.5 and 5.8 microg/mL, respectively. The MBC of UA-LIPO was twice as low (16 microg/mL) as that of UA (32 microg/mL). An improvement in the intracellular uptake of UA-LIPO was found (21.6 x 10(4) +/- 28.3 x 10(2) c.p.s), in comparison with UA (9.5 x 10(4) +/- 11.4 x 10(2) c.p.s). In addition, UA-LIPO remains much longer inside macrophages (30 hours). All data obtained from the encapsulation of usnic acid into liposomes as a drug delivery system (DDS) indicate a strong interaction between UA-liposomes and J774 macrophages, thereby facilitating UA penetration into cells. Considering such a process as ruling the Mycobacterium-transfection by magrophages, we could state that associating UA with this DDS leads to an improvement in its antimycobacterial activity.
authors.affiliation: Universidade Federal de Pernambuco, Laboratório de Imunopatologia Keizo-Asami, Recife-PE, Brazil.
authors.forename: Mariane C B
authors.initials: MC
authors.lastname: Lira
authors.forename: Marigilson P
authors.initials: MP
authors.lastname: Siqueira-Moura
authors.forename: Hercília M L
authors.initials: HM
authors.lastname: Rolim-Santos
authors.forename: Fábio C S
authors.initials: FC
authors.lastname: Galetti
authors.forename: Andreza R
authors.initials: AR
authors.lastname: Simioni
authors.forename: Noemia P
authors.initials: NP
authors.lastname: Santos
authors.forename: Eryvaldo S
authors.initials: ES
authors.lastname: Tabosa Do Egito
authors.forename: Célio L
authors.initials: CL
authors.lastname: Silva
authors.forename: Antônio C
authors.initials: AC
authors.lastname: Tedesco
authors.forename: Nereide S
authors.initials: NS
authors.lastname: Santos-Magalhães
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008081:Liposomes; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000254:growth & development*; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D001572:Benzofurans; D008081:Liposomes; C073339:usnic acid