<p>Azithromycin-liposomes as a novel approach for localized therapy of cervicovaginal bacterial infections</p>

Abstract

Background Efficient localized cervicovaginal antibacterial therapy, enabling the delivery of antibiotic to the site of action at lower doses while escaping systemic drug effects and reducing the risk of developing microbial resistance, is attracting considerable attention. Liposomes have been shown to allow sustained drug release into vaginal mucosa and improve delivery of antibiotics to bacterial cells and biofilms. Azithromycin (AZI), a potent broad-spectrum macrolide antibiotic, has not yet been investigated for localized therapy of cervicovaginal infections, although it is administered orally for the treatment of sexually transmitted diseases. Encapsulation of AZI in liposomes could improve its solubility, antibacterial activity, and allow the prolonged drug release in the cervicovaginal tissue, while avoiding systemic side effects. Purpose The objective of this study was to develop AZI-liposomes and explore their potentials for treating cervicovaginal infections. Methods AZI-liposomes that differed in bilayer elasticity/rigidity and surface charge were prepared and evaluated under simulated cervicovaginal conditions to yield optimized liposomes, which were assessed for antibacterial activity against several planktonic and biofilm-forming Escherichia coli strains and intracellular Chlamydia trachomatis, ex vivo AZI vaginal deposition/penetration, and in vitro cytotoxicity toward cervical cells. Results Negatively charged liposomes with rigid bilayers (CL-3), propylene glycol liposomes (PGL-2) and deformable propylene glycol liposomes (DPGL-2) were efficient against planktonic E. coli ATCC 700928 and K-12. CL-3 was superior for preventing the formation of E. coli ATCC 700928 and K-12 biofilms, with IC 50 values (concentrations that inhibit biofilm viability by 50%) up to 8-fold lower than those of the control (free AZI). DPGL-2 was the most promising for eradication of already formed E. coli biofilms and for treating C. trachomatis infections. All AZI-liposomes were biocompatible with cervical cells and improved localization of the drug inside vaginal tissue compared with the control. Conclusion The performed studies confirm the potentials of AZI-liposomes for localized cervicovaginal therapy.

Promising Drug Delivery Approaches to Treat Microbial Infections in the Vagina: A Recent Update

“…Biocompatibility study performed showed a slightly increased sensitivity of HeLa cells towards DPGLs as a notable lower concentration of monoacyl phosphatidylcholine was used with a short exposure time (24 h), suggesting less cytotoxic. Hence, it can be concluded that CLs is a potential dosage form for treatment of superficial infection and prevention of complicated infections while DPGLs are a promising approach for biofilm-related infections [ 71 ].…”

The Vaginal-PVPA: A Vaginal Mucosa-Mimicking In Vitro Permeation Tool for Evaluation of Mucoadhesive Formulations

“…This evidence highlights the potential of the chitosan-based formulation in providing adhesion to mucus and prolonging their resident time in loco. This increased retention of the formulation inside the vagina can especially be relevant in the case of recurrent bacterial vaginosis and infections related to biofilm formation [10]. The high degree of adhesion of the coated liposomes to the mucus layer on top of the PVPA barrier can result in a lower drug permeation due to the slower diffusion of the formulation through the mucus layer and the subsequent drug release farther from the permeation barrier when compared to plain liposomes.…”

“…So far, the in vitro models have been developed to predict (i) drug permeability in the vaginal environment (i.e., cell-based models, [ 2 ]) and (ii) to assess the mucoadhesive potential of the formulation in the vagina [ 5 , 8 ]. Moreover, efforts have been devoted to mimicking the fluids present in the vagina, such as the simulated vaginal fluid (SVF) proposed by Owen and Katz [ 9 ], which has been largely used to simulate the composition of vaginal fluids and test the diffusion and permeation of novel drug-delivery systems [ 5 , 6 , 10 ]. Even though the above-mentioned in vitro models and simulated fluid serve as great tools in developing formulations for vaginal administration, the lack of a reproducible, artificial, simple, and high throughput in vitro permeation model closely mimicking the vaginal mucosa and its environment was the reason for modifying the already established mucus-PVPA (Phospholipid Vesicle-based Permeation Assay) in vitro permeability model [ 11 ] to closely mimic these conditions.…”

Nanomedicine Fight against Antibacterial Resistance: An Overview of the Recent Pharmaceutical Innovations

“…For antibiotic delivery small unilamellar vesicles of ≃100 nm displayed high capability in the eradication of bacterial strains [34]. Liposomes proved to be useful for the management of topical [35], vaginal [36], pulmonary [37], and ocular [38] bacterial infections.…”