Structural Changes in the Lungs and Liver of Mice with Experimental Tuberculosis Treated with Liposome-Encapsulated Dextrazide

Male BALB/c mice were intravenously infected with Mycobacterium tuberculosis H37Rv (0.5 ml of 2-week culture). One month later, treatment with liposome-encapsulated dextrazide (LEDZ, a conjugate of isonicotinic acid hydrazide (INH) and 40 kDa oxidized dextran encapsulated in phosphatidylcholine liposomes), INH, or a combination of LEDZ with INH was started. The doses of LEDZ (liposome suspension) and INH were 0.025 ml/10 g body weight and 5 mg/kg body weight, respectively. All the substances were administered 2 times a week via inhalation or intraperitoneally (a total of 40 doses). We studied the number and the size of tuberculous granulomas, the size of destruction foci and inflammatory infiltrates in the lungs and liver, the amount of fibrous connective tissue, and the dynamic of these parameters. LEDZ+INH inhalations were most effective by the therapeutic ratios in comparison with inhalation and intraperitoneal injections of INH.