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Effect of enzymes on the degradation of thermosensitive copolymers for controlled release of drugs
Dávidíková, Anna Mária ; Michlovská, Lenka (oponent) ; Vojtová, Lucy (vedoucí práce)
Thermosensitive hydrogels used for drug delivery systems are of great interest these days. They serve as a drug vehicle that transport drugs to a target place and then they serve as a drug depot in the body. Hydrogels can be tuned to be able to encapsulate various drugs, to be sensitive to various external stimuli, or to degrade slower (maintain the drug longer in the body). To tune hydrogels, we need to know their degradation process and their behaviour in different degradation media; thus, we can predict how they will behave. In this proposed thesis, the degradations of various thermosensitive hydrogel solutions were studied in different degradation media. The theoretical part of this work provides a short review of thermosensitive hydrogels, their characterisation, properties, use for drug delivery systems, and degradation. Firstly, a triblock thermosensitive copolymer PLGA-PEG-PLGA that consists of poly(D,L-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D,L-lactic acid-co-glycolic acid) was synthesized via living ring-opening polymerization under an inert atmosphere and characterized via proton nuclear magnetic resonance spectroscopy and gel permeation chromatography. This copolymer was further used for hydrogel water solutions in 10, 15 and 20 wt. % concentrations. Hydrogel samples prepared at 37 were degraded in various media (UPW (ultrapure water), NaCl, PBS (phosphate-buffered saline), and PBS with enzyme) in the incubator for 30 days. The sample removal was set for 1, 2, 3, 7, 9, 14, 16, 21, 23 and 30 days except for the enzyme solution where we expected quick degradation. Degraded hydrogels were analysed via gel permeation chromatography and degradation media via liquid chromatography with mass spectroscopy. Gravimetric analysis and measurement of pH over time were also part of the hydrogel behaviour study. The last aim of this work was to evaluate the collected data and see whether the used enzyme affected the PLGA-PEG-PLGA hydrolytic degradation kinetics. The results proved a minor acceleration in the degradation by the enzyme. These results will serve as a foundation for further degradation studies.
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Effect of enzymes on the degradation of thermosensitive copolymers for controlled release of drugs
Dávidíková, Anna Mária ; Michlovská, Lenka (oponent) ; Vojtová, Lucy (vedoucí práce)
Thermosensitive hydrogels used for drug delivery systems are of great interest these days. They serve as a drug vehicle that transport drugs to a target place and then they serve as a drug depot in the body. Hydrogels can be tuned to be able to encapsulate various drugs, to be sensitive to various external stimuli, or to degrade slower (maintain the drug longer in the body). To tune hydrogels, we need to know their degradation process and their behaviour in different degradation media; thus, we can predict how they will behave. In this proposed thesis, the degradations of various thermosensitive hydrogel solutions were studied in different degradation media. The theoretical part of this work provides a short review of thermosensitive hydrogels, their characterisation, properties, use for drug delivery systems, and degradation. Firstly, a triblock thermosensitive copolymer PLGA-PEG-PLGA that consists of poly(D,L-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D,L-lactic acid-co-glycolic acid) was synthesized via living ring-opening polymerization under an inert atmosphere and characterized via proton nuclear magnetic resonance spectroscopy and gel permeation chromatography. This copolymer was further used for hydrogel water solutions in 10, 15 and 20 wt. % concentrations. Hydrogel samples prepared at 37 were degraded in various media (UPW (ultrapure water), NaCl, PBS (phosphate-buffered saline), and PBS with enzyme) in the incubator for 30 days. The sample removal was set for 1, 2, 3, 7, 9, 14, 16, 21, 23 and 30 days except for the enzyme solution where we expected quick degradation. Degraded hydrogels were analysed via gel permeation chromatography and degradation media via liquid chromatography with mass spectroscopy. Gravimetric analysis and measurement of pH over time were also part of the hydrogel behaviour study. The last aim of this work was to evaluate the collected data and see whether the used enzyme affected the PLGA-PEG-PLGA hydrolytic degradation kinetics. The results proved a minor acceleration in the degradation by the enzyme. These results will serve as a foundation for further degradation studies.
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