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Projects / Programmes source: ARIS

Nanomedicines with antibiotics and probiotics for local treatment of periodontal disease

Research activity

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 
Keywords
naofibers, drug delivery, probiotics, periodontal disease, oral microbiota
Evaluation (rules)
source: COBISS
Researchers (18)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  38497  PhD Maja Bjelošević Žiberna  Pharmacy  Researcher  2018 - 2022  79 
2.  11789  PhD Mirjana Gašperlin  Pharmacy  Researcher  2018 - 2022  600 
3.  29887  PhD Mirjam Gosenca Matjaž  Pharmacy  Researcher  2018 - 2022  142 
4.  17433  Tatjana Hrovatič    Technical associate  2018 - 2022 
5.  52126  PhD Marta Jagodic Hudobivnik  Chemistry  Researcher  2019 - 2022  131 
6.  18699  Mojca Keržan    Technical associate  2018 - 2022 
7.  24402  PhD Petra Kocbek  Pharmacy  Researcher  2018 - 2022  296 
8.  27733  PhD Tina Kosjek  Control and care of the environment  Researcher  2018 - 2022  360 
9.  09032  PhD Julijana Kristl  Pharmacy  Head  2018 - 2022  932 
10.  21408  PhD Aleš Lapanje  Microbiology and immunology  Researcher  2018 - 2022  355 
11.  34223  PhD Tijana Markovič  Pharmacy  Researcher  2018 - 2022  58 
12.  39199  PhD Janja Mirtič  Pharmacy  Junior researcher  2018 - 2020  56 
13.  07625  PhD Milan Petelin  Stomatology  Researcher  2018 - 2022  243 
14.  37548  PhD Tanja Potrč  Pharmacy  Researcher  2018 - 2022  43 
15.  27542  PhD Tomaž Rijavec  Microbiology and immunology  Researcher  2018 - 2022  248 
16.  23549  PhD Robert Roškar  Pharmacy  Researcher  2018 - 2022  305 
17.  30063  PhD Janja Snoj Tratnik  Control and care of the environment  Researcher  2018 - 2022  295 
18.  36439  PhD Špela Zupančič  Pharmacy  Researcher  2018 - 2022  128 
Organisations (3)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0787  University of Ljubljana, Faculty of Pharmacy  Ljubljana  1626973  17,246 
2.  0106  Jožef Stefan Institute  Ljubljana  5051606000  90,976 
3.  0312  University Medical Centre Ljubljana  Ljubljana  5057272000  77,744 
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.
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