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Projects / Programmes source: ARIS

Intra-pocket-targeted nanomedicines for 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
nanomedicines, chronic periodontitis, dental biofilm, metagenomics, probiotics
Evaluation (rules)
source: COBISS
Researchers (16)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  15490  PhD Pegi Ahlin Grabnar  Pharmacy  Researcher  2014 - 2017  212 
2.  15104  PhD Saša Baumgartner  Pharmacy  Researcher  2014 - 2015  306 
3.  32694  PhD Katarina Bolko Seljak  Pharmacy  Researcher  2014  55 
4.  11789  PhD Mirjana Gašperlin  Pharmacy  Researcher  2014 - 2017  600 
5.  29887  PhD Mirjam Gosenca Matjaž  Pharmacy  Researcher  2015 - 2017  142 
6.  18699  Mojca Keržan    Technical associate  2014 - 2017 
7.  24402  PhD Petra Kocbek  Pharmacy  Researcher  2014 - 2017  296 
8.  09032  PhD Julijana Kristl  Pharmacy  Head  2014 - 2017  932 
9.  21408  PhD Aleš Lapanje  Microbiology and immunology  Researcher  2014 - 2017  355 
10.  07625  PhD Milan Petelin  Stomatology  Researcher  2014 - 2017  243 
11.  14935  PhD Odon Planinšek  Pharmacy  Researcher  2014 - 2017  440 
12.  37548  PhD Tanja Potrč  Pharmacy  Researcher  2014 - 2017  43 
13.  07560  PhD Maja Remškar  Physics  Researcher  2014 - 2017  831 
14.  27542  PhD Tomaž Rijavec  Microbiology and immunology  Researcher  2014 - 2016  248 
15.  34432  PhD Ana Varlec  Energy engineering  Junior researcher  2015  29 
16.  36439  PhD Špela Zupančič  Pharmacy  Junior researcher  2014 - 2017  128 
Organisations (4)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0106  Jožef Stefan Institute  Ljubljana  5051606000  90,976 
2.  0312  University Medical Centre Ljubljana  Ljubljana  5057272000  77,744 
3.  0787  University of Ljubljana, Faculty of Pharmacy  Ljubljana  1626973  17,246 
4.  3351  Institute of Metagenomics and Microbial Technologies  Ljubljana  6554784  358 
Abstract
Chronic periodontitis is the most common periodontal disease, affecting majority of population over the age of 50. According to demographic changes in Europe, the number of patients is increasing. Currently available therapeutic approaches and medicines are only short-term effective, therefore, the comprehensive investigations of dental biofilm in relation to the disease pathogenesis, enabling development of innovative medicines for the permanent recovery, are necessary. The project will focus on the metagenomic analysis of bacterial communities and the development of a novel therapeutic approach based on optimisation of antimicrobial therapy and development of dosage forms with probiotics for targeted recolonisation of periodontal pockets. The research is based on a current treatment strategy and attempts to solve its shortcomings with an interdisciplinary approach, resulting in the development and proof of concept for long-term effective treatment of periodontal disease. The project aims to contribute to the understanding of the correlation between the composition and succession of biofilm formation and development of the disease. Newly acquired knowledge will be used in the development of nanomedicines and probiotics for targeted two-stage therapy. Development of the proposed concept will be based on the following work packages (WP): WP1. Metagenomic analysis of dental biofilm A protocol of sampling of biological material and the method of its treatment before metagenomic analysis will be developed. Metagenomics will be applied for investigation of biological samples obtained from patients with chronic periodontitis and healthy volunteers. The results will provide new knowledge about the composition and time dependant succession of biofilm formation. Further analysis is expected to generate correlations, that might explain the link between biofilm per se and the onset of the disease. WP2. Development of nanomedicine for intra-pocket-targeted delivery of antimicrobial drugs Novel nanotechnological approaches will be employed to develop effective nanomedicines with prolonged residence time at the target site and effective concentration of antibacterials. Nanoparticles and nanofibres based on biocompatible polymers will be investigated. Current strategy for the treatment will be followed, when selecting appropriate drug. WP3. Development of delivery system for probiotic The second part of the two-step treatment concept will be based on the application of a probiotic, which will recolonize tooth surface and encourage the formation of healthy biofilm. Probiotic strain of indigenous oral microbiota or commercially available probiotic will be selected and oral bioadhesive delivery system for its administration will be designed. WP4. Preparation of a model dental biofilm in vitro A cultivation method for selected bacteria will be developed for the preparation of an in vitro model of biofilm. It will be used for the preliminary evaluation of nanomedicines ​​and probiotics. The model of biofilm represents a platform for further testing of the proposed two-stage treatment of chronic periodontitis.   Relevance of the proposed research The vision of the project is not only the generation of new basic knowledge, but it represents an original approach for the treatment of periodontal disease. It involves the development of nanomedicines and formulations of probiotics for innovative two-stage treatment. The project will be carried out by an interdisciplinary team of experts in the field of stomatology, pharmacy and microbiology, which assures a high scientific relevance, creates a broad base of knowledge and provides access to the infrastructure necessary for project realization. The research will be based on experiences and lessons obtained in clinical practice, basic microbiological and pharmaceutical knowledge, and it will follow the need of the patients and society to improve the currently available treatment approaches.
Significance for science
Current therapy of periodontal disease has been proven to be long-term ineffective, since the disease often reoccurs. According to research, the disease is manifestation of the imbalance in multiple factors, which normally maintain the healthy periodontal tissues. Our research is based on understanding of the disease pathology and current treatment strategy with the aim to solve its shortcomings with the interdisciplinary approach based on development of nanomedicines for long-term cure. Here, metagenomic approach was applied for study of bacteria community succession in the oral cavity of healthy individuals and periodontal disease patients to enable controlled colonization of oral niches. The acquired knowledge was implemented in the design and development of nanomedicines with antibiotics and orally effective probiotics. A step forward was made in development of structurally different nanofibers for prolonged release of antibiotic in therapeutic concentrations, indicating their potential to achieve a therapeutic effect. The nanosized and bioadhesive properties of nanofibers can increase the retention of delivery system in the periodontal pockets, where antibiotic is released in prolonged manner. Thus, this reduces the patient's burden with systemic antibiotic doses and the risk of adverse effects, including the development of bacterial resistance. The results obtained represent an important step forward in the development of local nanodelivery systems, which can address social challenges associated with the emergence of resistant bacteria. Furthermore, we have demonstrated oral microbiota to be a valuable source of potential new probiotic strains whose therapeutic administration can result in reestablishment of healthy dental biofilm. First, we have developed methods for isolation and identification of bacteria that could be widely used for the analysis of various biological samples with a low content of DNA. The new bacterial strains were isolated from the oral biofilm of healthy volunteers and those with the best antimicrobial action against periodontal pathogens were incorporated into the delivery system (nanofibers, microcapsules) for administration into the periodontal pockets. We have proven that electrospinning as well as microencapsulation, if properly controlled, enable the production of delivery system with probiotics. The incorporation of probiotics in the form of spores represents an innovative approach, which assures a high bacterial viability during the production and storage. In addition to new knowledge and numerous novel nanofiber formulations, we also developed new methods, which enabled: (i) sampling and analysis of biological samples with low-bacterial content, (ii) electrospinning of complex systems with drugs or probiotics, and (iii) evaluation of drug release in experimental conditions that resemble the periodontal pocket (newly developed in vitro method). The project demonstrated the applicability of new methods in generation of key data in the development and optimization of nanomedicines. We anticipate that in the future they could shorten the time and reduce the expenses of other local delivery system development. The project results were published in 10 scientific articles and 3 were submitted for publication in journals with high impact factors. Additionally, they were presented as 4 invited lectures and 24 contributions at scientific conferences. The project revealed that developed delivery systems with antibiotics and probiotics provide an excellent starting point for further development of two-stage periodontal disease treatment.
Significance for the country
The pharmaceutical industry has a great socio-economic impact in every country. It produces high quality, safe and effective medicines and medical devices and competes with them in the domestic and the global markets. Our research is directed towards the improvement of the competitiveness of the Slovenian economy. The new knowledge gained in the project can be implemented in the development of medicines and wider, enabling faster development of advanced medicines for targeted treatment of periodontal disease. The project is in line with the draft of Slovenia's Development Strategy 2014-2020, highlighting the need for closer integration between the various players (research, education, and business sector) for the faster transfer of knowledge and innovations in to the practice and on the market, especially in areas consistent with the development priorities of the country. Solving societal challenges and helping to bridge the gap between research and the market are amongst the high priority objectives of Horizon 2020, indicating that our proposed project is consistent also with the vision of the European Union development. In terms of innovation, we have patented a newly developed release device, which leads to the possibility of marketing knowledge and products to already established enterprises as well as establishment of new small “spin-off” companies. Our project thus fulfilled one of the fundamental objectives of the development strategy of the European Community and Slovenia i.e. the direct transfer of knowledge from academia to industry. The number of people with periodontal disease has increased due to aging population (75 % of people older than 65 suffers from periodontal disease) and their treatment requires chronic therapy, associated with high cost of treatment. The novel concept developed in this project is based on the formulation of nanomedicines for two-stage therapy, which is a starting point for the further development of clinically useful medicine and therapeutic approach that will actively interfere with the course of the disease and regeneration of periodontal tissues. Therefore, higher effectiveness of the therapy and lower treatment costs are expected. Furthermore, this therapeutic approach will improve the treatment compliance in patients and quality of their life. Finally, the proposed research addresses an issue of responsible use of antibiotics, since it suggests local administration of antimicrobial in the form of nanomedicine, which is expected to reduce the risk of bacterial resistance development as well as reduce the incidence of other resistant-bacteria, associated infectious diseases, which are consequently difficult to cure. The achievements of the research project were presented to several national and international scientific conferences, thus promoting Slovenia and the Slovenian Science.
Most important scientific results Annual report 2014, 2015, final report
Most important socioeconomically and culturally relevant results Annual report 2014, 2015, final report
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