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Bakterier som är resistenta mot antibiotika har de senaste åren blivit ett stort hot mot mänskligheten. Att utveckla nya antibiotikaläkemedel är väldigt tidskrävande samt kommer med en dyr prislapp. Det är några av anledningarna att forskare har inriktat sig på antimikrobiella peptider (AMPs) som ett alternativ till traditionella antibiotika. Dessa peptider finns i alla levande organismer och uppvisar en snabb och ospecifik mekanism. Vidare så är de mindre benägna att utveckla resistens hos bakterierna. Däremot så har dessa AMPar visat sig ha låg stabilitet och en del toxiska biverkningar. Olika typer av nanobärare kan användas för att överkomma dessa kommakortanden. Syftet med denna studie var att utveckla en optimerad nanobärare för AMPen AP114. Peptiden har blivit inkluderad i nanostrukturerade lipidbärare (NLC) samt liposomer. Dessa har producerats med smält emulsifieringsmetod och lösningsinjektion metoden. De fysikalkemiska karaktäristik hos olika blanka samt AP115 laddade nanoformuleringar har analyserats samt jämförts. Resultaten indikerade att liposomformuleringarna hade den lägsta partikelstorleken och storleksfördelning men en kontrollerad in vitro frisättning av peptiden över 48 timmar. Generellt, så indikerar de preliminära resultaten en potential nanoformulering för peptiden AP114. / In the past few years, bacterial resistance to antibiotics has posed a major threat to humankind. Development of substitutes for traditional antibiotics is a highly time consuming and expensive venture. For this reason, researchers are focusing on using antimicrobial peptides (AMP) as an alternate. These peptides are found in all living organisms and exhibit a fast and non-targeted mechanism of action. Besides, they are less susceptible to microbial resistance. However, these therapeutic peptides are not stable and have toxic side effects. To overcome these limitations, drug delivery systems have been explored. In this study, the aim was to develop an optimized drug delivery system for AP114. The peptide has been encapsulated in nanostructured lipid carriers (NLC) and liposomes, produced by melt emulsification method and solvent injection method, respectively. The physicochemical characterization of different blank and AP114 loaded nanoformulations were analyzed and compared. The results indicated the liposome samples to have the lowest particle size distribution and polydispersity, with a controlled in vitro release of the peptide over 48 hours. Overall, these preliminary findings suggest a promising potential for the formulation of a nanocarrier for AP114 peptide.

Noble metal nanoparticles such as gold and silver are of interest because of the unique electro-optical properties (e.g., localized surface plasmon resonance [LSPR]) that originate from the collective behavior of their surface electrons. These nanoparticles are commonly developed and used for biomedical and industrial application. A recent report has predicted that the global market for gold nanoparticles will be over 12.7 tons by year 2020. However, these surface-functionalized nanoparticles can be potential environmental persistent contaminants post-use due to their high colloidal stability in the aquatic systems. Despite, the environmental risks associated with these nanoparticles, just a few studies have investigated the effect of nanofeature factors such as size and shape on the overall fate/transport and organismal uptake of these nanomaterials in the aquatic matrices. This study presents a comprehensive approach to evaluate the colloidal stability, fate/transport, and organismal uptake of these nanoparticles while factoring in the size and shape related properties. We demonstrate the importance and effect of anisotropicity of a gold nanoparticle on the colloidal behavior and interaction with ecologically susceptible aquatic biota. We also show how readily available characterization techniques can be utilized to monitor and assess the fate/transport of this class of nanoparticles. We further describe and investigate the relationship between the aspect ratio (AR) of these elongated gold nanoparticles with clearance mechanisms and rates from the aquatic suspension columns including aggregation, deposition, and biopurification. We illustrate how a fresh water filter-feeder bivalve, Corbicula fluminea, can be used as a model organism to study the size and shape-selective biofiltration and nanotoxicity of elongated gold nanoparticles. The results suggest that biofiltration by C. fluminea increases with an increase in the size and AR of gold nanoparticle. We develop a simple nanotoxicity assay to investigate the short-term exposure nanotoxicity of gold nanoparticles to C. fluminea. The toxicity results indicate that for the tested concentration and exposure period that gold nanoparticles were not acutely toxic (i.e., not lethal). However, gold nanoparticles significantly inhibited the activities of some antioxidant enzymes in gill and digestive gland tissues. These inhibitions could directly affect the resistance of these organisms to a secondary stressor (temperature, pathogens, hypoxia etc.) and threaten organismal health. / Ph. D.

The thesis is focused on the research of stability of controlled drug release systems based on a blend of plasticized starch/polycaprolactone (TPS/PCL) that served as a carrier. Antibiotic vancomycin was used as a model drug, and its release from TPS/PCL pellets into aqueous environment was followed by UV-spectroscopy and the obtained time dependences were treated by a simple kinetic model. Moreover, the simultaneous release of starch particles to the surrounding liquid phase was studied by static and dynamic light scattering as well as transmission electron microscopy (TEM) in order to obtain information on the stability of biodegradable matrix and on the structure of the products of the pellet decomposition on a nanoscale level. Key words: vancomycin, starch, drug delivery system, polycaprolactone (PCL), particle release, dynamic light scattering (DLS), static light scattering (SLS)

Předkládaná diplomová práce se zabývá extrakcí nanočástic oxidu titaničitého z produktů osobní péče, konkrétně opalovacích krémů a následnou charakterizací těchto částic. Počet komerčně dostupných produktů s obsahem nanočástic TiO2 se neustále zvyšuje a to se sebou přináší potřebu vyhodnotit potenciální osud a nepřímou expozici TiO2 nanošástic o různých velikostí a tvarů a zkoumat jejich celý životní cyklus. Bylo zkoumáno použití ultrafiltrace a ultracentrifugace jako extrakční metody. Dvě metody pro extrakci TiO2 nanočástic byly vyvinuty a aplikovány na vzorky opalovacích krémů. Extrahované částice mohou být použity pro ekotoxikologické studie, případně experimenty v mesokosmu. Velikost částic byla stanovena pomocí metody dynamického rozptylu světla a transmisní elektronové mikroskopie.