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Modification of thermosensitive copolymer with bioactive substances for medical applications
Debnárová, Simona ; Vojtová, Lucy (oponent) ; Michlovská, Lenka (vedoucí práce)
Biodegradable synthetic polymers bring many advantages over other materials for the utilization in the field of regenerative medicine and tissue engineering. The most important advances involve the capability of optimalizing mechanical or chemical properties and the degradation kinetics. Especially polyesters are interesting because of their simple biodegradation. They undergo the hydrolysis of ester linkage and the degradation products are metabolized without harmful effects. Diploma thesis is focused on synthetic biodegradable PLGA-PEG-PLGA triblock copolymers based on poly(lactic acid) (PLA), poly(glycolic acid) (PGA) and poly(ethylene glycol) (PEG) that belong to the group of biodegradable polyesters. The content of hydrophilic and hydrophobic parts of polymer chain induces the amphiphilic character. Prepared triblock copolymers are capable of forming hydrogel by physical cross-linking in consequence of their amphiphilic character. These materials have noticed significant interest in the field of medical sciences. Theoretical part describes hydrogels, physical cross-linking of amphiphilic block copolymers and the mechanisms of degradation. Description of PLGA-PEG-PLGA triblock copolymers is divided on PLGA copolymers, PEG and their physico-chemical properties. Reliable knowledge of chemical functionalization by succinic anhydride, folic acid and itaconic anhydride is presented. Dopamine is introduces as a linker and the most important bioactive substances are mentioned. Experimental part presents certain methods of synthesis that lead to functionalization and modification of PLGA-PEG-PLGA triblock copolymers. Functionalization by itaconic anhydride was proceeded to obtain functionalized copolymer with both ends capped by reactive double bonds and carboxylic groups. The double bonds enable to form chemical cross-links and the end-capped carboxylic groups offer the opportunity to modify it by biologically active compounds. The modification by bioactive substances L-lysine and butylamine enriches the polymer network and linker dopamine provides the versatility of attached bioactive substances, their stabilization and the maintenance of its biological activity. Final products were characterized by the means of 1H NMR, FTIR and DRA analysis. Functionalization was carried out in a bulk with higher amount of bonded itaconic acid 79.4 mol % and subsequent modifications were proceeded in aqueous solution, organic solution or in a bulk. The most effective method of modification was synthesis in organic solution with solvent N,N-dimethylformamide with activating system dicyclohexylcarbodiimide and 4-(dimethylamino)pyridine. The highest amount of bonded dopamine was 18.6 mol %, the highest amount of attached butylamine was 7.8 mol % and L-lysine was not bonded at all.
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Modification of thermosensitive copolymer with bioactive substances for medical applications
Debnárová, Simona ; Vojtová, Lucy (oponent) ; Michlovská, Lenka (vedoucí práce)
Biodegradable synthetic polymers bring many advantages over other materials for the utilization in the field of regenerative medicine and tissue engineering. The most important advances involve the capability of optimalizing mechanical or chemical properties and the degradation kinetics. Especially polyesters are interesting because of their simple biodegradation. They undergo the hydrolysis of ester linkage and the degradation products are metabolized without harmful effects. Diploma thesis is focused on synthetic biodegradable PLGA-PEG-PLGA triblock copolymers based on poly(lactic acid) (PLA), poly(glycolic acid) (PGA) and poly(ethylene glycol) (PEG) that belong to the group of biodegradable polyesters. The content of hydrophilic and hydrophobic parts of polymer chain induces the amphiphilic character. Prepared triblock copolymers are capable of forming hydrogel by physical cross-linking in consequence of their amphiphilic character. These materials have noticed significant interest in the field of medical sciences. Theoretical part describes hydrogels, physical cross-linking of amphiphilic block copolymers and the mechanisms of degradation. Description of PLGA-PEG-PLGA triblock copolymers is divided on PLGA copolymers, PEG and their physico-chemical properties. Reliable knowledge of chemical functionalization by succinic anhydride, folic acid and itaconic anhydride is presented. Dopamine is introduces as a linker and the most important bioactive substances are mentioned. Experimental part presents certain methods of synthesis that lead to functionalization and modification of PLGA-PEG-PLGA triblock copolymers. Functionalization by itaconic anhydride was proceeded to obtain functionalized copolymer with both ends capped by reactive double bonds and carboxylic groups. The double bonds enable to form chemical cross-links and the end-capped carboxylic groups offer the opportunity to modify it by biologically active compounds. The modification by bioactive substances L-lysine and butylamine enriches the polymer network and linker dopamine provides the versatility of attached bioactive substances, their stabilization and the maintenance of its biological activity. Final products were characterized by the means of 1H NMR, FTIR and DRA analysis. Functionalization was carried out in a bulk with higher amount of bonded itaconic acid 79.4 mol % and subsequent modifications were proceeded in aqueous solution, organic solution or in a bulk. The most effective method of modification was synthesis in organic solution with solvent N,N-dimethylformamide with activating system dicyclohexylcarbodiimide and 4-(dimethylamino)pyridine. The highest amount of bonded dopamine was 18.6 mol %, the highest amount of attached butylamine was 7.8 mol % and L-lysine was not bonded at all.
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