In-vitro anti-chlamydial activities of free and liposomal tetracycline anddoxycycline

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 (CA L), anionic (ANL) and neutral (NTL) liposomes by sonication, were quantifie d by high-performance liquid chromatography, Anti-chlamydial activities wer e 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 Chlamyd ia trachomatis L-2/434/Bu (10(3) ifu/well). After incubation for 72 h at 37 degrees C, chlamydial inclusions were stained by the May-Grunwald Giemsa m ethod to establish MICs. MBCs were determined in chlamydial agent-free medi um 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 S EM 0.3% in anionic (ANL-Tet) and 2.2 SEM 0.6% in neutral (NTL-Tet) liposome s; no Tet was detected in cationic (CAL-Tet) liposomes, MIC values were 0.0 6 mg/L for Dox, 0.12 mg/L for Tet, 0.03 mg/L for CAL-Dox, NTL-Dox and NTL-T et, 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 a nd NTL-Tet. For MICs, the relative increase in antichlamydial activity obse rved with liposomal formulations compared to the corresponding free antibio tic 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 encap sulated than Tet in all liposomes. Liposome-encapsulated drugs showed great er anti-chlamydial activities than their free forms; thus, these drug formu lations have potential in the treatment of chlamydial infections.