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J Med Microbiol. 1999 Jul;48(7):689-93.

In-vitro anti-chlamydial activities of free and liposomal tetracycline and doxycycline.

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Department of Microbiology and Immunology, University of Montreal, Quebec, Canada.


The purpose of this study was to evaluate the anti-chlamydial activities in vitro of liposome-encapsulated doxycycline (Dox) and tetracycline (Tet) in comparison with free Dox and Tet. Dox and Tet encapsulated in cationic (CAL), anionic (ANL) and neutral (NTL) liposomes by sonication, were quantified by high-performance liquid chromatography. Anti-chlamydial activities were determined by addition of serial dilutions of antibiotics (MIC 0.12-0.007 mg/L; MBC 4-0.25 mg/L) to HeLa 229 cell monolayers inoculated with Chlamydia trachomatis L2/434/Bu (10(3) ifu/well). After incubation for 72 h at 37 degrees C, chlamydial inclusions were stained by the May-Gr├╝nwald Giemsa method to establish MICs. MBCs were determined in chlamydial agent-free medium after second passages. Dox-encapsulation efficiencies were 28.6 SEM 6.4% in cationic (CAL-Dox), 49.1 SEM 6.7% in anionic (ANL-Dox) and 21.0 SEM 0.8% in neutral (NTL-Dox) liposomes. Tet-encapsulation efficiencies were 3.5 SEM 0.3% in anionic (ANL-Tet) and 2.2 SEM 0.6% in neutral (NTL-Tet) liposomes; no Tet was detected in cationic (CAL-Tet) liposomes. MIC values were 0.06 mg/L for Dox, 0.12 mg/L for Tet, 0.03 mg/L for CAL-Dox, NTL-Dox and NTL-Tet, and 0.01 mg/L for ANL-Dox and ANL-Tet. MBCs were 4 mg/L for Tet, 0.5 mg/L for CAL-Dox and NTL-Dox, and 1 mg/L for Dox, ANL-Dox, ANL-Tet, NTL-Tet and NTL-Tet. For MICs, the relative increase in anti-chlamydial activity observed with liposomal formulations compared to the corresponding free antibiotic ranged from 2- to 6-fold with Dox and from 4- to 10-fold with Tet. For MBCs, the relative increases in anti-chlamydial activity were 2- and 4-fold with liposome-encapsulated Dox and Tet, respectively. Dox was better encapsulated than Tet in all liposomes. Liposome-encapsulated drugs showed greater anti-chlamydial activities than their free forms; thus, these drug formulations have potential in the treatment of chlamydial infections.

[Indexed for MEDLINE]

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