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Projects / Programmes source: ARIS

Elecrospun nanofibrous materials for solid state drug delivery system

Research activity

Code Science Field Subfield
2.05.02  Engineering sciences and technologies  Mechanics  Experimental mechanics 

Code Science Field
T000  Technological sciences   

Code Science Field
2.03  Engineering and Technology  Mechanical engineering 
Keywords
electrospinning, drug delivery, bimodal polyamid 6, polymer, pore size distribution
Evaluation (rules)
source: COBISS
Researchers (16)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  33907  PhD Alexandra Aulova  Mechanics  Researcher  2016 - 2019  95 
2.  33756  PhD Marko Bek  Mechanics  Researcher  2016 - 2019  170 
3.  14575  PhD Maja Čemažar  Oncology  Researcher  2016 - 2019  1,438 
4.  04316  PhD Igor Emri  Mechanics  Head  2016 - 2019  1,281 
5.  30976  PhD Marina Gergesova  Mechanics  Researcher  2016 - 2017  36 
6.  11122  PhD Albin Kristl  Pharmacy  Researcher  2016 - 2019  350 
7.  52425  Elzbieta Krol    Technical associate  2018 - 2019 
8.  24559  PhD Anatolij Nikonov  Materials science and technology  Researcher  2016  264 
9.  29212  Pavel Oblak    Technical associate  2016  80 
10.  34373  PhD Maša Omerzel  Medical sciences  Researcher  2016  200 
11.  35754  PhD Alen Oseli  Mechanics  Researcher  2017 - 2018  139 
12.  26530  PhD Andraž Perhavec  Medical sciences  Researcher  2016 - 2019  141 
13.  36247  Alenka Rogelj Ritonja    Technical associate  2016 - 2017 
14.  23549  PhD Robert Roškar  Pharmacy  Researcher  2016 - 2019  309 
15.  08800  PhD Gregor Serša  Oncology  Researcher  2016 - 2019  1,520 
16.  22659  PhD Simon Žakelj  Pharmacy  Researcher  2016 - 2019  162 
Organisations (4)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0302  Institute of Oncology Ljubljana  Ljubljana  5055733000  15,789 
2.  0782  University of Ljubljana, Faculty of Mechanical Engineering  Ljubljana  1627031  29,569 
3.  0787  University of Ljubljana, Faculty of Pharmacy  Ljubljana  1626973  17,414 
4.  3084  Institute for Sustainable Innovative Technologies, EEIG  Ljubljana  2224577000 
Abstract
The project addresses establishment of electrospinning needle-free technology of biocompatible bimodal polyamide 6 that will be used for manufacturing containers for Solid State Drug Delivery approach. This approach utilizes polymeric electrospun nanofibrous materials as a shell material for drug carrier containers for targeted chemotherapy of localized tumors and prolonged drug release needed in case of chronic diseases. Possibility to control drug release rate is a crucial factor of the proposed approach and can be achieved via changes of pore size distribution of the membrane and degradability rate of a polymer. Biodegradability rate as well as its effect on pore size distribution PSD depends on chemical composition of the polymer and its structure. Patented biocompatible multimodal polyamide 6 is chosen for this project because of its outstanding biocompatibility and extremely high sensitivity to strain-rate, temperature and pressure variation during the production process. These properties allow forming gradient structure of a solid material using injection-molding technique, as well as gradient nano-fibers manufactured with electrospinning process. In this case strain-rate of the pulling of polymer solution by electrostatic field will result in different fiber structure, which will directly influence the rate of biodegradability. Pore size distribution (PSD) depends only on the technological process of electrospinning, which establishment is the goal of the proposed project. PSD depends on fiber diameter, and membrane thickness, which in turn are determined by parameters of manufacturing process (solution composition, air conditioning,...). In line with this, the goal of the proposed project is to determine interrelation between fiber diameter and membrane thickness that affect pore size and pore size distribution, and electrospinning processing parameters for multimodal polyamide 6. Investigation of the solution composition, its viscosity, electrical conductivity and surface tension properties, effect of electrostatic field on the electrospinning process, quality and diameter of the formed fibers will be performed. In addition structural analysis of the fibers will be done. Materials with different pore size distributions, in order to study effect of membrane thickness and fiber diameter, will be manufactured and their pore size distribution will be measured and confirmed by the diffusion tests on model drugs.
Significance for science
The goal of the proposed project is to understand the process of nano-fiber formation in a needle-free free-surface electrospinning process. This knowledge will be used for establishment of the repeatable production of nano-purouse membranes needed in development of the new innovative solid-state drug delivery system.   Clasical nozzle electrospinning technology is relatively well understood, on the other hand there is very little known about the new needle-free free-surface electrospinning process. In particular there is no knowledge about the behavior of bio-compatible multimodal polyamides, which could open completely “new chapter” in cancer treatment. In line with this the project will contribute to: i) Understanding of physics governing needle-free electrospinning process. Compared to classical electrospinning using nozzle where Taylor cone is formed by electrical field on the surface of the drop, in needle-free engineering solution the Taylor cone forms on the string wetted with polymer solution, therefore parameters of surface tension and electrical conductivity required for a stable electrospinning of the same polymer solution can significantly differ. The obtained relations will provide basis for guidelines for electrospinning using needle-free technology. The main advantage of this process is that it excludes parts that can be clogged and require attention and allows manufacturing electrospun material on industrial scales.   ii) Understanding behavior of multimodal polyamide 6 during such a complex process as electrospinning. It is known from the literature that molecular weight of the polymer used affects electrospinning process significantly, mostly due to its direct influence on viscosity of the solution. Multimodal polyamide 6 already demonstrated its outstanding properties in relation to formation of various structures depending on temperature and pressure boundary conditions. The project will show effect of pulling rate on the fiber structure formation. This information can be used for formation of membranes with various absorptive properties and biodegradation rates.   iii) Knowledge on formation of pore size distributions of nanofibrous materials prepared by electrospinning. In particular we are interested how fiber diameter and membrane thickness affects the average pore size, and pore size distribution.   Developed knowledge will be published in renowned journals and, most important, used for development of new generation solid-state drug delivery system for cancer treatment. Developed technology will be protected with international patents.
Significance for the country
The proposed project has great potential for enabling breakthrough applications in the medical and other industries. It provides the basis for the development and production of stand-alone applications (e.g. antibacterial filter for air filtration, etc.) as well as complex solutions, such as the ultimate goal of this line of research i.e. the solid state drug delivery system. The diverse range of possibilities that stem from this new technology provides a broad appeal for utilization by many companies of different sizes, both in Slovenia and on the global market. One such company is the co-financer of the project Fresenius Kabi (FK), a global health company specialized in medicine and technologies for infusion, transfusion and clinical nutrition.   Future development and spin-off Through this project FK will gain the capability to design and develop (with the help of project partners) a new generation of medical systems – the aforementioned solid state drug delivery system. Other breakthrough applications such as e.g. intraoperative mats, will be developed through a dedicated spin-off company after the end of the project.   Co-financing In light of this future development potential FK will co-finance 25% of the project, while other partners, who will further collaborate in the post-project spin-off, will invest through other forms of contribution – the CEM and ISIT research groups will provide the use of patented knowledge on effects of temperature and pressure during processing of bimodal polyamide 6, the Saratov State University will provide expertise and insight on electrospinning procedures on Nanospider technology and the BASF will provide their excusive and patented material. The non monetary value of these contributions matches in size the extent of the financial co-financing by FK.   Direct social impact The result of the project will improve existing clinical techniques for cancer treatment, drug delivery reliability for patients with chronic diseases and also lead to the creation of new therapeutic systems based on advanced medical devices. The application of such system will increase the efficiency of numerous medical treatments and will also reduce both treatment time and cost. This will directly translate to overall lower healthcare costs, shorter convalescence through a higher effectiveness of treatment of cancer and chronic diseases, while also significantly improving the patients’ comfort.   Direct broader industrial impact Nanospider electrospinning and bimodal polyamide 6 are both futureproof technologies, which enable the development and production of the high added-value products in a multitude of industries. Alongside medical use scenarios, possible applications range from filtration materials, textiles to materials with specific properties (ultraviolet resistant, antibacterial, heat resistant, etc.). Another great aspect of both these technologies is the fact that they are easily scalable once their specific parametrization is established.
Most important scientific results Interim report, final report
Most important socioeconomically and culturally relevant results Interim report, final report
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