Liposomal Encapsulation Increases the Efficacy of Azithromycin against Chlamydia trachomatis.

Anita Bogdanov,Zsuzsanna Cseh,László Janovák,Dezső P Virok,Sunčanica Ljubin-Sternak,Katalin Burián,Jasmina Vraneš,Valéria Endrész,Željka Vanić,Tomislav Meštrović

doi:10.3390/pharmaceutics14010036

Abstract

Chlamydia trachomatis (C. trachomatis) is an obligate intracellular bacterium linked to ocular and urogenital infections with potentially serious sequelae, including blindness and infertility. First-line antibiotics, such as azithromycin (AZT) and doxycycline, are effective, but treatment failures have also been reported. Encapsulation of antibiotics in liposomes is considered an effective approach for improving their local effects, bioavailability, biocompatibility and antimicrobial activity. To test whether liposomes could enhance the antichlamydial action of AZT, we encapsulated AZT in different surface-charged elastic liposomes (neutral, cationic and anionic elastic liposomes) and assessed their antibacterial potential against the C. trachomatis serovar D laboratory strain as well as the clinical isolate C. trachomatis serovar F. A direct quantitative polymerase chain reaction (qPCR) method was used to measure chlamydial genome content 48 h post infection and to determine the recoverable chlamydial growth. All the liposomes efficiently delivered AZT to HeLa 229 cells infected with the laboratory Chlamydia strain, exhibiting the minimal inhibitory concentrations (MIC) and the minimal bactericidal concentrations (MBC) of AZT even 4–8-fold lower than those achieved with the free AZT. The tested AZT-liposomes were also effective against the clinical Chlamydia strain by decreasing MIC values by 2-fold relative to the free AZT. Interestingly, the neutral AZT-liposomes had no effect on the MBC against the clinical strain, while cationic and anionic AZT-liposomes decreased the MBC 2-fold, hence proving the potential of the surface-charged elastic liposomes to improve the effectiveness of AZT against C. trachomatis.

Highlights

C. trachomatis ocular and urogenital serovars are responsible for the acute and chronic inflammations of ocular and urogenital mucosal surfaces
The neutral AZT-liposomes had no effect on the minimal bactericidal concentrations (MBC) against the clinical strain, while cationic and anionic AZT-liposomes decreased the MBC 2-fold, proving the potential of the surface-charged elastic liposomes to improve the effectiveness of AZT against C. trachomatis
We have previously found that elastic liposomes were more effective in delivering AZT to the C. trachomatis infected HeLa cells than conventional liposomes with rigid bilayers, their activity was lower than the free drug

Summary

Introduction

C. trachomatis ocular and urogenital serovars are responsible for the acute and chronic inflammations of ocular and urogenital mucosal surfaces. The chronic inflammation could lead to serious complications, such as blindness and infertility. Health Organization report, 44 countries are affected by trachoma, 137 million people are at risk of the infection and 1.9 million people suffer from infection-related impaired vision. Pharmaceutics 2022, 14, 36 or blindness [1]. C. trachomatis-caused sexually transmitted infections are estimated to be acquired by 131 million people annually, where mostly young (16–24 years-old) people are affected. 1,758,668 and 406,406 cases of chlamydia infection were reported in 2018 in the USA and in 26 European countries, respectively [2]. The macrolide antibiotic AZT inhibits protein synthesis by irreversibly binding to the

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