Nanofibers for codelivery of selected microbiota cocktails and antimicrobials for local treatment of vaginal infections




01. October 2022 - 30. September 2025


0,56 FTE


Špela Zupančič


1-09 Natural sciences and Mathematics - Pharmacy

Research Organisation:







Scientific background and problem identification. Vaginal infections are the most common reason women seek medical help and can cause serioushealth consequences, such as pelvic inflammatory disease, increased risk of sexually transmitted infections, and adverse pregnancy outcomes. Themost common vaginal infections are bacterial vaginosis and vaginal candidiasis, both characterized by changes in vaginal microbiota composition.The population of Lactobacillus spp. that predominate in healthy microbiota is decreased due to the anaerobic bacteria or Candida spp. overgrowth.Current treatments with antimicrobials are largely ineffective and result in disease recurrence, and the consequential spread of antimicrobialresistance. We believe that due to recent breakthrough findings in the field of microbiota per se and its relation to these diseases, it is time toinvestigate and develop alternative therapeutic approaches to efficiently combat such microbiota-related diseases with live biotherapeutic products.
State-of-the art. An important step in the treatment of vaginal infections is seen by the use of beneficial bacteria, such as lactobacilli, which candecrease the number of pathogens via several mechanisms, including competition for binding sites, and release of antimicrobial substances. Up-to-date meta-analysis has revealed only moderate efficacy of lactobacilli in the treatment of vaginal infections, which appears to be due to the use oflactobacilli isolated from gut microbiota or fermented foods, as these do not colonise the vaginal surfaces beyond the treatment period. Despite theknown history of use of gut microbiota-isolated lactobacilli, the newest regulatory framework of live biotherapeutic products requires in-depth safetyevaluation and elucidation of the mechanism of action of novel live therapeutic bacterial strains. Also, the available formulations have severallimitations, thus, intravaginal application of lactobacilli selected from autochthonous vaginal microbiota using a patient-friendly delivery system isexpected to be more efficient.
Project objectives. The objective is to develop highly innovative mucoadhesive nanofibers loaded with lactobacillus cocktail and antimicrobial forlocal treatment of vaginal infections. This comprehensive solution will involve selection and characterisation of relevant vaginal lactobacilli obtainedfrom healthy women, including identification of their metabolites and evaluation of their antimicrobial and immunomodulatory activity. Furthermore,optimal lactobacillus cocktail possessing synergistic antimicrobial activity will be incorporated into nanofibers with and without an antimicrobialdrug. The physicochemical and biological properties of designed nanofibers will be characterised in detail in vitro with developed methodsresembling conditions in the vagina, and in vivo in an animal model. Cutting-edge technologies based on fluorescence imaging will be used for closetracking of lactobacilli release from the nanofibers, their growth and proliferation. This will be possible due to our expertise in genetic modificationof the selected lactobacilli to express fluorescent proteins. Work programme and implementation. All essential steps, covered by the project, are systematically organised into five interconnected Work Packages, to achieve the final goal. This will be implemented by an interdisciplinary project consortium including experts from the fields of pharmaceutical nanotechnology (Faculty of Pharmacy, University of Ljubljana), biotechnology (Institut Jožef Stefan), clinical microbiology (National Laboratory of Health, Environment and Food) and gynaecology (University Medical Centre Ljubljana), with already established collaborations and necessary knowledge and infrastructure for implementation of the project. The results will be disseminated, and the innovative principles can be applied for the future development of other similar live biotherapeutic products.



Bibliographical references, arising directly from the implementation of the project:


Financed by:

Research projects (co)funded by the Slovenian Research Agency.