Unexploited potential of polyelectrolytes for the development of advanced delivery systems of drugs and probioticsMirtič, Janja (Avtor) Kristl, Julijana (Mentor) zdravilne učinkovineprobiotikiparodontalne boleznizdravljenjealginatkompleksiranjenanodelcinanovlaknaelektrostatsko sukanjePolyelectrolytes are polymers whose repeating units carry groups that can be ionized, making the polymers charged. The main objective of this doctoral dissertation was to resolve the challenges of utilising polyelectrolytes, in the development of advanced delivery systems for drugs and probiotic bacteria. The focus was on polyelectrolytes that originate from nature (i.e., polysaccharides: alginate, chitosan) that are biocompatible and biodegradable, with a primary objective of periodontal disease treatment. Periodontal disease is an inflammatory disease primarily caused by the microbial imbalance. Current therapeutic approaches lead only to short-term recovery, thus there is a need for the development of novel treatments that would reduce the periodontal plaques, reestablish oral microbial balance, modulate the immune response, and regenerate the periodontal tissues. In the first part, polyelectrolyte complexation of alginate with different crosslinkers as a method of nanoparticle formation is thoroughly investigated and described. We showed that nanoparticle formation is spontaneous, led by entropy, even when different classes of crosslinkers are used. The class of crosslinker is affecting the molar ratio of the components at which nanoparticles are formed as well as their characteristics. Completely novel surfactant-polyelectrolyte-complex nanoparticles were investigated further, where the cooperative interaction between the surfactant - cetylpyridinium chloride, and polyelectrolyte - alginate, was proven. These cetylpyridinium-alginate nanoparticles were further utilised for increasing water solubility of ibuprofen, where distinct nanoparticle substructures were shown for the first time. In the second part, nanofibers with a high proportion of alginate in composition were successfully electrospun. With the addition of high molecular weight poly(ethylene oxide), blend solutions of appropriate rheological and conductometric properties were made, that enabled electrospinning. Using multivariate analysis and by varying different solution parameters the nanofiber diameter could be finely tuned to produce scaffolds useful in regenerative medicine. The last section focused on bacterial cell entrapment, as single cells with a layer-by-layer deposition method, or as the incorporation of probiotics into alginate microcapsules. In the first case, different polyelectrolytes were tested, and stimulated emission depletion microscopy was utilized for the first time to visualize the effects of polyelectrolyte layering on bacteria. These were, contrary to the expectation, mainly dependent on the bacterial strain used, and not on the polyelectrolyte properties. Alginate microcapsules for probiotic incorporation were made by prilling and followed lyophilisation, with additional chitosan coating. Such microcapsules presented a novel probiotic delivery system that enabled their survival during processing and storage, their revival and activity. Thus, such a system could serve as an efficient probiotic delivery system into the periodontal pockets. This doctoral dissertation is defining new knowledge on the topics of polyelectrolyte complexation, electrospinning of polysaccharides and encapsulation of bacterial cells that will enable wider use of polyelectrolytes for development of advanced delivery systems for drugs and probiotics.[J. Mirtič]20202022-06-01 12:04:37Doktorska disertacija137111sl