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Program-controlled freeze drying for the preparation of the delivery system of native hyaluronan and hydrophobic molecules
Waczulíková, Kristína ; Sedláček, Petr (referee) ; Enev, Vojtěch (advisor)
The amphiphilic nature of the hyaluronan biopolymer facilitates interactions between its hydrophobic portions of the chain and the hydrophobic ligands, making it one of the promising compounds that can be used as a suitable carrier for drug delivery. Therefore, the aim of this diploma work was by means of a program-controlled freeze-drying to prepare a system based on native hyaluronan, which would be capable of transporting hydrophobic drugs. Perylene, pyrene, prodan and 1,6-diphenyl-1,3,5-hexatriene fluorescence probes were used as model compounds to simulate hydrophobic drug-hyaluronan interactions. Freeze-drying efficiency was studied using infrared spectrometry and scanning electron microscopy. ATR-FTIR spectrometry confirmed for all probes but pyrene the hydrophobic interactions between the hyaluronan and probe molecules based on the presence of the C=C bond valence vibration absorption band in the aromatic probe rings. From the IR spectra, it was not possible to confirm with certainty the presence of residual tert-butyl alcohol in the samples. SEM photographs revealed that increasing the pressure during drying process had a positive effect on the quality of the lyophilized sample in the second series of samples. Interactions of individual fluorescent probes with hyaluronan were studied using steady-state and time-resolved fluorescence spectrometry. Positive results have been obtained, indicating the presence of fluorescent probes interacting with the hydrophobic regions of the hyaluronan chains. The results of this work can contribute to the development of carrier systems in the field of targeted drug distribution.
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Program-controlled freeze drying for the preparation of the delivery system based on hyaluronan and real drugs
Řihák, Marek ; Sedláček, Petr (referee) ; Enev, Vojtěch (advisor)
The aim of this thesis was to prepare native hyaluronan-based carrier systems using the lyophilisation as a suitable method to ensure an interaction between certain drugs and the polymeric structure which would lead to an increased solubility of hydrophobic drugs. For the preparation of such a system the tert-butyl alcohol was used as a co-solvent with the ability to support hydrophobic effect between the drug and a hydrophobic domain of hyaluronan. Since all polar domains of hyaluronan are located in the equatorial position, the axial position is occupied by hydrogens and therefore the molecule gains the amphiphilic character. Previous studies have confirmed that freeze-drying is a useful method for a carrier system preparation. However, this study focuses on the preparation of such systems with samples of real drugs, which were previously replaced by fluorescence sondes. Since all drug samples have good fluorescence characteristics, the fluorescence spectroscopy was used as the main method to determine the success of the preparation. Other methods included a thermogravimetric analysis and the infrared spectroscopy with Fourier transformation. All the mentioned methods have confirmed that lyophilisation is a useful method for the preparation of the carrier systems with real drugs. Great results have been achieved in the terms of the solubility of freeze-dried systems. In the last step, the co-solvent residues were determined by head-space solid phase microextraction. This method also provided some valuable information and confirmed that tert-butyl alcohol could be found in the lyophilised systems only on very low levels.
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Program-controlled freeze drying for the preparation of the delivery system of native hyaluronan and hydrophobic molecules
Waczulíková, Kristína ; Sedláček, Petr (referee) ; Enev, Vojtěch (advisor)
The amphiphilic nature of the hyaluronan biopolymer facilitates interactions between its hydrophobic portions of the chain and the hydrophobic ligands, making it one of the promising compounds that can be used as a suitable carrier for drug delivery. Therefore, the aim of this diploma work was by means of a program-controlled freeze-drying to prepare a system based on native hyaluronan, which would be capable of transporting hydrophobic drugs. Perylene, pyrene, prodan and 1,6-diphenyl-1,3,5-hexatriene fluorescence probes were used as model compounds to simulate hydrophobic drug-hyaluronan interactions. Freeze-drying efficiency was studied using infrared spectrometry and scanning electron microscopy. ATR-FTIR spectrometry confirmed for all probes but pyrene the hydrophobic interactions between the hyaluronan and probe molecules based on the presence of the C=C bond valence vibration absorption band in the aromatic probe rings. From the IR spectra, it was not possible to confirm with certainty the presence of residual tert-butyl alcohol in the samples. SEM photographs revealed that increasing the pressure during drying process had a positive effect on the quality of the lyophilized sample in the second series of samples. Interactions of individual fluorescent probes with hyaluronan were studied using steady-state and time-resolved fluorescence spectrometry. Positive results have been obtained, indicating the presence of fluorescent probes interacting with the hydrophobic regions of the hyaluronan chains. The results of this work can contribute to the development of carrier systems in the field of targeted drug distribution.
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