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Enkapsulace léčiv v termocitlivých micelárních gelech
Smolková, Miroslava ; Pavliňáková, Veronika (oponent) ; Chamradová, Ivana (vedoucí práce)
Předložená diplomová práce se zabývá enkapsulací hydrobobního léčiva Sulfathiazolu (STA) v termosenzitivním hydrogelu, které je tvořeno amfifilními vláknitými molekulami kopolymeru poly(laktid-co-glykolid)-blok-poly(ethylen glykol)-blok-poly(laktid-co-glykolidu) (PLGA-PEG-PLGA). V experimentální části práce byla důkladně popsána struktura micel, která je závislá na koncentraci výchozího kopolymeru. K rozměrové charakterizaci micelární velikosti ve vodném roztoku byla použita metoda dynamického rozptylu světla (DLS). Zároveň zobrazovací technika transmisní elektronové mikroskopie s kryogenní úpravou vzorku (Cryo-TEM) potvrdila přechod ze sférických micel do vláknitých rozvětvených struktur s řadou topologických interakcí. Změna viskoelastických vlastností micelárního hydrogelu po přidání STA byla studována pomocí reologické analýzy. Studovaný triblokový kopolymer se zdá být vhodným materiálem v oblasti tkáňového inženýrství jako nosič v aplikacích pro cílené doručování léčiv a regeneraci tkání.
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Ring-opening Polymerization of Lactones and Lactides
Boháčová, Zdeňka ; Cihlář, Jaroslav (oponent) ; Lehocký,, Marián (oponent) ; Vojtová, Lucy (vedoucí práce)
Biodegradable aliphatic polyesters based on polylactones, polylactides and their copolymers are particularly interesting for their applications in the medical field. The major polymerization method used to synthesize these polymers has been the ring-opening polymerization (ROP) of lactones or lactides. Many organometallic compounds are effective initiators for the controlled ROP synthesis of polyesters but heavy metals derivatives are harmful for the human organisms. There has been an increasing interest in the development of efficient "green" catalytic systems for the synthesis of biodegradable aliphatic polyesters. This thesis is dedicated to the synthesis of aliphatic polyesters based on polycaprolactone, polylactide and polyglycolide and especially their copolymers using organic catalyst from the group of free N-heterocyclic carbenes (NHC) without the central heavy metal atom. A literature review is focused on the recent advances in the ROP of lactones and lactides using organic metal-free catalysts. However, there is no evidence of using carbenes for ROP synthesis of polyglycolide or its copolymers. An experimental part of this work briefly describes the preparation and properties of 1,3-di-tert-butylimidazol-2-ylidene (NHC-tBu) free carbene from its stable chloride salt. The next section is focused on the preparation of polyesters from cyclic ester monomers, namely L lactide, D,L-lactide, glycolide and -caprolactone using NHC-tBu catalyst. In particular, novel synthesis of thermosensitive amphiphilic triblock copolymers based on hydrophobic biodegradable polylactide, polyglycolide and biocompatible hydrophilic polyethylene glycol (PLGA–PEG–PLGA) using prepared NHC-tBu has been investigated. Consequently, influences of reaction conditions (i.e. monomers purification, reaction temperature, type of solvent, solvent to monomer ratio and initiator to catalyst ratio) have been evaluated. Finally, the comparison of PLGA–PEG–PLGA copolymers prepared using NHC-tBu and Sn(II)2-ethylhexanoate catalysts has been performed. It was demonstrated that combination of NHC-tBu with PEG creates the effective catalytic system for ring opening polymerization of lactone or lactides. Polymers were prepared with the high conversion of monomer (70 – 85%) and low polydispersity index (Mw/Mn at around 1.2). PLGA–PEG–PLGA copolymer with two phase transitions (sol-gel and gel-suspension) and gelation temperature between 35 – 43 °C was obtained. In most cases, changes in the reaction conditions did not have significant influence on chemical properties such as molecular weight or polydispersity index, however essentially affected the physical properties such as visco-elastic behaviors.
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Enkapsulace léčiv v termocitlivých micelárních gelech
Smolková, Miroslava ; Pavliňáková, Veronika (oponent) ; Chamradová, Ivana (vedoucí práce)
Předložená diplomová práce se zabývá enkapsulací hydrobobního léčiva Sulfathiazolu (STA) v termosenzitivním hydrogelu, které je tvořeno amfifilními vláknitými molekulami kopolymeru poly(laktid-co-glykolid)-blok-poly(ethylen glykol)-blok-poly(laktid-co-glykolidu) (PLGA-PEG-PLGA). V experimentální části práce byla důkladně popsána struktura micel, která je závislá na koncentraci výchozího kopolymeru. K rozměrové charakterizaci micelární velikosti ve vodném roztoku byla použita metoda dynamického rozptylu světla (DLS). Zároveň zobrazovací technika transmisní elektronové mikroskopie s kryogenní úpravou vzorku (Cryo-TEM) potvrdila přechod ze sférických micel do vláknitých rozvětvených struktur s řadou topologických interakcí. Změna viskoelastických vlastností micelárního hydrogelu po přidání STA byla studována pomocí reologické analýzy. Studovaný triblokový kopolymer se zdá být vhodným materiálem v oblasti tkáňového inženýrství jako nosič v aplikacích pro cílené doručování léčiv a regeneraci tkání.
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Ring-opening Polymerization of Lactones and Lactides
Boháčová, Zdeňka ; Cihlář, Jaroslav (oponent) ; Lehocký,, Marián (oponent) ; Vojtová, Lucy (vedoucí práce)
Biodegradable aliphatic polyesters based on polylactones, polylactides and their copolymers are particularly interesting for their applications in the medical field. The major polymerization method used to synthesize these polymers has been the ring-opening polymerization (ROP) of lactones or lactides. Many organometallic compounds are effective initiators for the controlled ROP synthesis of polyesters but heavy metals derivatives are harmful for the human organisms. There has been an increasing interest in the development of efficient "green" catalytic systems for the synthesis of biodegradable aliphatic polyesters. This thesis is dedicated to the synthesis of aliphatic polyesters based on polycaprolactone, polylactide and polyglycolide and especially their copolymers using organic catalyst from the group of free N-heterocyclic carbenes (NHC) without the central heavy metal atom. A literature review is focused on the recent advances in the ROP of lactones and lactides using organic metal-free catalysts. However, there is no evidence of using carbenes for ROP synthesis of polyglycolide or its copolymers. An experimental part of this work briefly describes the preparation and properties of 1,3-di-tert-butylimidazol-2-ylidene (NHC-tBu) free carbene from its stable chloride salt. The next section is focused on the preparation of polyesters from cyclic ester monomers, namely L lactide, D,L-lactide, glycolide and -caprolactone using NHC-tBu catalyst. In particular, novel synthesis of thermosensitive amphiphilic triblock copolymers based on hydrophobic biodegradable polylactide, polyglycolide and biocompatible hydrophilic polyethylene glycol (PLGA–PEG–PLGA) using prepared NHC-tBu has been investigated. Consequently, influences of reaction conditions (i.e. monomers purification, reaction temperature, type of solvent, solvent to monomer ratio and initiator to catalyst ratio) have been evaluated. Finally, the comparison of PLGA–PEG–PLGA copolymers prepared using NHC-tBu and Sn(II)2-ethylhexanoate catalysts has been performed. It was demonstrated that combination of NHC-tBu with PEG creates the effective catalytic system for ring opening polymerization of lactone or lactides. Polymers were prepared with the high conversion of monomer (70 – 85%) and low polydispersity index (Mw/Mn at around 1.2). PLGA–PEG–PLGA copolymer with two phase transitions (sol-gel and gel-suspension) and gelation temperature between 35 – 43 °C was obtained. In most cases, changes in the reaction conditions did not have significant influence on chemical properties such as molecular weight or polydispersity index, however essentially affected the physical properties such as visco-elastic behaviors.
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