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Polymerní nanoformulace pro léčbu vnitrobuněčných infekcí: Vývoj, charakterizace strukutry a analýza / Beating Intracellular Bacterial Infections with Polymeric Nanobead-Based Interventions: Development, Structure Characterization, and AnalysisTrousil, Jiří January 2020 (has links)
One hundred years after the discovery of antimicrobials and antibiotics, intracellular bacterial pathogens remain a major cause of global morbidity and mortality. This is due to the complex and intricate ability of these pathogens to undergo intracellular replication while evading host cell immune defense. Bacterial agents such as Legionella pneumophila, Francisella tularensis, and Mycobacterium tuberculosis, as the causative agents of Legionnaires' disease, pulmonary tularemia, and tuberculosis (TB), respectively, contribute to this burden. Moreover, these agents are weaponizable pathogens due to their aerosolizability. TB represents a global health problem, although a potentially curative therapy has been available for approximately 50 years; this intracellular disease affects approximately 1 in 3 people worldwide, with over 10 million new cases per year and one death every three minutes. TB can usually be treated with a 6- to 9-month course of combined therapy. The necessity of using a cocktail of anti-TB drugs and the long-term treatment schedules required for conventional therapy, however, result in poor patient compliance; therefore, the risk of treatment failure and relapses is higher. Hence, improved drug delivery strategies for the existing drugs can be exploited to shorten the duration of TB...
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Ordered Structures from Nanoparticles/Block Copolymer Hybrids: Ex-situ Approaches toward Binary and Ternary NanocompositesHorechyy, Andriy 01 July 2011 (has links)
Within the field of modern technology, nanomatrials, such as nanoparticles (NP), nanorods (NR), quantum dots (QD) etc. are, probably, the most prominent and promising candidates for current and future technological applications. The interest in nanomaterials arise not only form the continuous tendency towards dimensions minimisation of electronic devices, but also due to the fact, that new and, often, unique properties are acquired by the matter at the length scale between 1 and 100 nm.
The ability to organize nanoparticles into ordered arrays extends the range of useful NP-based systems that can be fabricated and the diversity of functionalities they can serve. However, in order to successfully exploit nanoparticle assemblies in technological applications and to ensure efficient scale-up, a high level of direction and control is required.
Recently, block copolymers (BCP) have attracted much attention as a powerful and very promising tool for creation of nanoscale ordered structures owing to their self-assembling properties. In addition, these systems offer the possibility to fabricate nanostructured composite materials via incorporation of certain nanoadditives (i.e. NPs). The concept is that by selective inclusion of the nanoparticles into one of the blocks of a self-assembling copolymer, the nanoparticles are forced into a defined spatial arrangement determined by the phase morphology of the block copolymer.
In present work self-assembling phenomena of block copolymers was exploited to fabricate binary (NP/BCP) and ternary (NP1/NP2/BCP) composites, filled with pre-synthesized nanoparticles of various nature. Polystyrene-block-polyvinylpyridine block copolymers (PS-b-PVP) of various composition and molecular weight were used for fabrication of nanocomposites.
The first part of the thesis focuses on fabrication of functional BCP-based composites containing magnetic nanoparticles (MNP), selectively assembled within one of the blocks of BCP matrix. Magnetic nanoparticles (MNPs) were selected among others since, as for today, there is the least number of successful results reported in literature on their selective incorporation into one of the phases of a BCP matrix. From the application point of view fabrication of periodic arrays of “magnetic domains” with periodicity on nanometer scale is also of interest for potential use in high-density magnetic data storage devices.
For this purpose, ferrite-type MNP (Fe3O4, CoFe2O4) having apparent affinity toward polyvinylpyridine (PVP) phase were prepared using simple one-pot synthesis. Highly selective nanoparticles segregation into PVP domains of BCP was achieved owing to the presence of sparse stabilizing organic shell on the nanoparticles surface. Importantly, as-prepared MNPs did not require any additional surface modification step to acquire affinity towards PVP phase. Appropriate selection of annealing conditions allowed to produce patterns of nearly perfect degree of lateral order over relatively large surface large area (more than 4 sq µm).
The second task of present work was fabrication of ternary NP1/NP2/BCP hybrid composites with two different types of nanoparticles being selectively localized in different microdomains of phase segregated block copolymer matrix. So far as only few studies have been reported on developing of approaches toward ternary composites, creation of alternative and straight forward routes toward such systems is still a challenge.
In the frame of this part of present work, silver nanoparticles (AgNPs) covered with polystyrene shell were prepared, with the purpose to be incorporated into polystarene phase of phase separated PS-b-PVP block copolymer matrix.
Two different approaches were tested to achieve desired three-component system. First, supposed simple blending of block copolymer and two kinds of nanoparticles having specific affinity toward different blocks of BCP in common solvent. After preparation of MNP/AgNP/BCP composite thin film and subsequent solvent vapour annealing, different domains of microphase segregated PS-b-PVP BCP were filled with different type of nanoparticles.
Alternatively, step-wise approach for nanoparticles incorporation was developed and implemented for successful selective nanoparticles incorporation. For this purpose polystyrene stabilized AgNPs (i.e. NP1) were initially mixed with PS-b-PVP BCP to produce composite thin films having nanoparticles selectively located within PS microdomains, while citrate-stabilized second type nanoparticles (i.e NP2) were deposited from their aqueous solutions into PVP domains of AgNP/PS-b-PVP composites.
By partition of nanoparticles incorporation procedure into two distinct steps it was also possible to increase effective loading of each type of NPs into BCP matrix.
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