Projects / Programmes
Nanomedicines with antibiotics and probiotics for local treatment of periodontal disease
| Code |
Science |
Field |
Subfield |
| 1.09.00 |
Natural sciences and mathematics |
Pharmacy |
|
| Code |
Science |
Field |
| B740 |
Biomedical sciences |
Pharmacological sciences, pharmacognosy, pharmacy, toxicology |
| Code |
Science |
Field |
| 3.01 |
Medical and Health Sciences |
Basic medicine |
naofibers, drug delivery, probiotics, periodontal disease, oral microbiota
Researchers (18)
Organisations (3)
Abstract
Periodontal disease is perhaps the most common of human afflictions, and through its local and systemic effects, it can considerably deteriorate the overall quality of person’s life. Periodontal disease is a biofilm-induced chronic inflammation of the periodontium, where two factors are specifically linked with its pathogenesis: (i) a shift in the oral microbiota (i.e., dysbiosis) that results in a reduction in the beneficial symbionts and/or an increase in the periodontal pathogens; and (ii) a destructive host immune response that leads to degradation of the periodontium. All of the treatment approaches available today only result in temporary improvement of the disease status, or only in a temporary ‘cure’, as after treatment, periodontopathogens frequently recolonise the oral niches, including the periodontal pockets, and thus trigger relapse of the disease.
Here, our interdisciplinary consortium has been put together to propose an innovative concept of periodontal disease treatment, with the involvement of experts from the fields of pharmaceutical nanotechnology (Faculty of Pharmacy, University of Ljubljana), microbiology (Institut ‘Jozef Stefan’) and dental medicine (University Medical Centre Ljubljana). Our access to current cutting-edge research equipment provides us with a good starting point for the success of the proposed Project. Our goal is to develop and characterise new nanomedicines for comprehensive two-stage local therapy. For the first stage of therapy, nanofibre-based medicine with dual activity will be developed (i.e., antibiotic and immunomodulatory) to simultaneously eradicate periodontopathogens and regulate the host immune response. Thus, oral niches will be formed that will be colonised in a controlled manner in the second stage of therapy, using characterised indigenous bacteria as an oral probiotic incorporated into nanofiber.
The Project aims to achieve the following main outcomes:
1. Develop well-characterised polymer nanofibres with a combination of a selected antibiotic and an immunomodulatory drug incorporated.
2. Characterise new probiotic strains from among our isolates from indigenous oral microbiota, and select a safe combination of potential probiotic strains with the most potent antibiotic activity against periodontal pathogens tested in vitro.
3. Develop nanofibres that incorporate the combination of probiotics that show characteristics that are promising for restoration of the normal oral microbiota.
4. Prepare a bacterial ‘bio-microfactory’ that is based on nanofibres for the local delivery of antibacterial metabolites as an alternative to classical antibiotics delivery.
Our proposed innovative treatment concept currently represents a hot topic, and will provide an important step forward towards addressing the three identified key challenges associated with the efficacy of any periodontal disease treatment: namely, the limited efficacy of available antibiotic therapies, the poorly explored field of probiotics derived from indigenous oral microbiota, and the generally temporary ‘cure’ of periodontal disease. Our results will provide fundamentals for more powerful fight with this widespread disease.
Significance for science
The new discoveries about the pathogenesis of periodontal disease present an important basis for development of novel therapeutic approaches. Here proposed the two-stage therapy of periodontal disease will influence on all three of the main factors associated with its pathogenesis; namely, the presence of periodontopathonic bacteria, the inadequate immune response, and the microbial dysbiosis, which will lead to more effective treatment and thus to improvement of the patient’s quality of life. This represents an entirely new concept, since all of the present treatment protocols target more or less only one factor involved. Our Project will be based on current treatment strategy and will try to solve some of its apparent shortcomings, with the aim being to progress towards a long-term cure. The latest findings and discoveries in the fields of nanodelivery systems, clinical pharmacology, and metagenomics will be implemented in the design and development of the nanofibers loaded with antimicrobial and immunomodulatory drugs or probiotics. Thus, new knowledge will be generated and scientific questions will be answered, such as following:
- Is it possible to control the release of two different drugs, namely an antibiotic and an immunomodulatory drug, when incorporated in electrospun nanofibers?
- How do the polymer matrix in nanofibers and the environmental conditions influence bacterial activation and outgrowth?
- Can probiotics in water-insoluble nanofibers represent a ‘bio-microfactory’ for local, prolonged production of antimicrobial agents?
- Are bacterial strains isolated from indigenous oral microbiota, which show significant antibacterial activities against periodontal pathogens in vitro, safe for in-vivo application?
- How do potential new probiotic strains respond to interactions with periodontal pathogens and other members of the oral microbiota?
- Is the incorporation of two different probiotic strains into nanofibers beneficial over a single probiotic strain?
As the topic that the Project is addressing is highly interdisciplinary, the expected contribution to science is going to be distributed among three main scientific areas: drug delivery, microbiology, and dental science. Furthermore, the new methods resembling periodontal pocket developed and validated in scope of the project will be applicable not only in the case of nanomedicenes for periodontal disease, but for all medicines for application in biological microenvironments with small volumes of medium (e.g. wounds). The project is indirectly solving also problems of bacterial resistance to antibiotics, since the risk of bacterial resistence is expected to be lower in case of antibiotic treatment with nanomedicines and local delivery. In addition, our in water-insoluble nanofibers presenting a ‘bio-microfactory’ of antimicrobial agents may present more powerful tool against bacterial resistance. Thus, scientific and practical value of the Project results are expected to be significant.
Significance for the country
The new discoveries about the pathogenesis of periodontal disease present an important basis for development of novel therapeutic approaches. Here proposed the two-stage therapy of periodontal disease will influence on all three of the main factors associated with its pathogenesis; namely, the presence of periodontopathonic bacteria, the inadequate immune response, and the microbial dysbiosis, which will lead to more effective treatment and thus to improvement of the patient’s quality of life. This represents an entirely new concept, since all of the present treatment protocols target more or less only one factor involved. Our Project will be based on current treatment strategy and will try to solve some of its apparent shortcomings, with the aim being to progress towards a long-term cure. The latest findings and discoveries in the fields of nanodelivery systems, clinical pharmacology, and metagenomics will be implemented in the design and development of the nanofibers loaded with antimicrobial and immunomodulatory drugs or probiotics. Thus, new knowledge will be generated and scientific questions will be answered, such as following:
- Is it possible to control the release of two different drugs, namely an antibiotic and an immunomodulatory drug, when incorporated in electrospun nanofibers?
- How do the polymer matrix in nanofibers and the environmental conditions influence bacterial activation and outgrowth?
- Can probiotics in water-insoluble nanofibers represent a ‘bio-microfactory’ for local, prolonged production of antimicrobial agents?
- Are bacterial strains isolated from indigenous oral microbiota, which show significant antibacterial activities against periodontal pathogens in vitro, safe for in-vivo application?
- How do potential new probiotic strains respond to interactions with periodontal pathogens and other members of the oral microbiota?
- Is the incorporation of two different probiotic strains into nanofibers beneficial over a single probiotic strain?
As the topic that the Project is addressing is highly interdisciplinary, the expected contribution to science is going to be distributed among three main scientific areas: drug delivery, microbiology, and dental science. Furthermore, the new methods resembling periodontal pocket developed and validated in scope of the project will be applicable not only in the case of nanomedicenes for periodontal disease, but for all medicines for application in biological microenvironments with small volumes of medium (e.g. wounds). The project is indirectly solving also problems of bacterial resistance to antibiotics, since the risk of bacterial resistence is expected to be lower in case of antibiotic treatment with nanomedicines and local delivery. In addition, our in water-insoluble nanofibers presenting a ‘bio-microfactory’ of antimicrobial agents may present more powerful tool against bacterial resistance. Thus, scientific and practical value of the Project results are expected to be significant.
Most important scientific results
Interim report
Most important socioeconomically and culturally relevant results
