|
|
Synthesis and Characterization of Multifunctionalized Biodegradable Copolymers
Michlovská, Lenka ; Petrůj, Jaroslav (oponent) ; Lehocký,, Marián (oponent) ; Vojtová, Lucy (vedoucí práce)
This dissertation summarizes the current state-of-the-art in the field of biodegradable thermosensitive copolymers, which in the form of aqueous sol at room temperature change to gel at body temperature. These polymer materials are useful in medicine for injection application as drug carriers or resorbable implants for tissue regeneration. In experimental work, thermosensitive amphiphilic triblock copolymers based on hydrophobic biodegradable polylactide and polyglycolide and biocompatible hydrophilic polyethylene glycol (PLGA–PEG–PLGA) were synthesized using vacuum line apparatus. Prepared PLGA–PEG–PLGA copolymer with two phase transitions from sol-gel and gel-suspension was subsequently modified with itaconic anhydride. The resulting functionalized ITA/PLGA–PEG–PLGA/ITA copolymer contains at both ends of chains reactive double bonds suitable for further polymerization or crosslinking and functional carboxyl group for possible modification by biological active substances. Physical and chemical crosslinking were also investigated in terms of the ratio of hydrophilic and hydrophobic chains and with a view of the amount of bounded itaconic acid. Prepared aqueous solutions of synthesized ITA/PLGA–PEG–PLGA/ITA copolymer change to a gel at the temperature between 33 and 43 °C. The evaluated critical gel concentration and the critical gel temperature was 6 % w/v and 34 °C, respectively, for the copolymer with PLGA/PEG ratio equal to 2.5. When the copolymer was more hydrophobic, then start of gelation became earlier and gel was more hydrolytically stable. Gel stiffness increased with increasing PLGA/PEG ratio and it depends on methods and type of solvent used during purification of copolymer. Prepared ITA/PLGA–PEG–PLGA/ITA copolymers were crosslinked using blue light without further crosslinker. Hydrolytical stability of ITA modified samples was significantly improved and increased in direct proportion with the both increasing time of crosslinking and the amount of double bonds attached to polymer chains. Sample having 63 % of ITA crosslinked for 40 mins fully degraded in water after 32 days. By proton NMR relaxometry it was found that while the sample has been swelled in water (after 12 hours) the amount of unbonded water reduces and gradually diffuses into cavities on the surface of sample and slowly changed to both weakly bonded water and strongly bonded water to polymer chains. Weakly bonded water began release from sample and changed back to the free water, when sample start to degrade and nodes and gel network begin to break. However, the thermal stability of chemically crosslinked samples increased only up to 20 minutes of crosslinking time where approximately 57 % of double bonds of itaconic acid (at 1640 cm-1) were transformed to the new single RR'C–CHR'' bonds at 795 cm-1ones by making crosslinks proved by ATR-FTIR. Longer crosslinking time (above 30 minutes) led to changes in chemical structure by beta-scission of chain and partially by recombination of double bonds. Rediscovery of new double bonds in different place of the chain reduced both the thermal stability and glass transition temperature from 242 °C to 237 °C and from -2.2 to -5.8 °C, respectively. The proposed thesis shows how the polymer composition, modification by functional groups and physical conditions affect either the physical or the chemical crosslinking of prepared amphiphilic copolymers.
|
|
|
Functionalization of biodegradable polymers by itaconic anhydride
Michlovská, Lenka ; Hermanová, Soňa (oponent) ; Vojtová, Lucy (vedoucí práce)
Presented diploma thesis describes preparation of biodegradable termosensitive triblock copolymer based on poly(ethylene glycol), poly(lactic acid) and poly(glycolic acid) (PLGA-PEG-PLGA) that was subsequently modified by itaconic anhydride (ITA), which gives copolymer both reactive double bonds and functional carboxylic acid groups essential for the reaction with biological active material. The general goal was optimizing reaction conditions in order to reach the highest yield of ITA end-capped to polymer resulting in ITA/PLGA-PEG-PLGA/ITA copolymer. Prepared functionalized copolymer as a component of heterogeneous composite e.g. with hydroxyapatite might be suitable for biomedical application in the field of tissue engineering as a temporary replacement or adhesive of hard tissues (bones). In the theoretical part, hydrogels, their separation, crosslinking and degradation mechanism are generally described together with physico-chemical properties and the synthesis of the individual used biomaterials and their copolymers, itaconic anhydride and its functionalization. The experimental part describes in detail the synthesis of PLGA-PEG-PLGA copolymer via ring opening polymerization (ROP) using vacuum line and Schlenk’s techniques. Kinetics of the ROP was measured and optimization of polymerization conditions was suggested. Prepared thermosensitive copolymer was additionally modified by itaconic anhydride via catalytic ring-opening reaction. Optimization of ITA functionalization conditions were evaluated in terms of effect temperature, time, ITA purification and presence of the solvent effect. Successful end-capping of PLGA-PEG-PLGA copolymer by ITA was precisely characterized by means of 1H NMR, FT-IR and GPC methods. Kinetics of PLGA-PEG-PLGA copolymerization from unsublimated (neat) and sublimated (purified) D,L-lactide and glycolide were studied. In both cases the synthesis proceeded in a bulk at 130 °C for 3 hours with conversion approximately of 90 %. Prolonged polymerization period had no effect on the increase of conversion. In the case of ROP using unsublimated monomers, a rapid increase of monomer conversion was observed during first few minutes, followed by constant progress. Resulting copolymer displayed molecular weight of 7155 g/mol and narrow polydispersity index of 1.26. Optimal conditions were reached when sublimated monomers were polymerized. First, increase of conversion up to 88 % was nearly linear (living polymerization) to 2.5 hours, after that a plateau was observed. Well-defined PLGA-PEG-PLGA copolymer with molecular weight of 7198 g/mol and narrow polydispersity index of 1.20 was obtained. Optimal conditions for synthesis of ITA/PLGA-PEG-PLGA/ITA copolymer were reached with sublimated itaconic anhydride in a bulk at the temperature of 110 °C with total reaction time of 1.5 hours. As a result 76.6 mol. % of ITA was end-capped to the original PLGA PEG PLGA copolymer. Resulting molecular weight of ITA/PLGA-PEG-PLGA/ITA copolymer (5881 g/mol) with polydispersity index of 1.37 found by GPC correlated well with Mn calculated from 1H NMR and a theoretical Mn (Mn(theor)/Mn(GPC)/Mn(NMR) = 1/0.89/0.96).
|
|
|
Modification of PLA using reactive extrusion
Matláková, Jana ; Petrůj, Jaroslav (oponent) ; Kučera, František (vedoucí práce)
Diploma thesis deals with grafting of maleic anhydride and itaconic anhydride onto the poly(lactic acid) (PLA). The dependence of conversion on the various molar ratios of monomer to initiator was observed on the modified poly(lactic acid) at the temperatures 180 °C and 200 °C. The amount of grafted monomer was determined due to the acido-basic titration and due to the FT-IR spectroscopy. Effect of grafting value on the crystallinity modified PLA was determined by using differential scanning calorimetry, DSC. Degradation of PLA was observed orientation due to the melting flow index, MFI.
|
|
|
Příprava materiálů na bázi reaktivně modifikovaných polyolefinů
Běťák, Lukáš ; Žídek, Jan (oponent) ; Kučera, František (vedoucí práce)
Diplomová práce popisuje přípravu modifikovaných polyolefinů roubováním anhydridem kyseliny itakonové a následnou reakcí s primárními anebo sekundárními aminy (diaminododekan, aminoethylethanolamin a aminoethylpiperazin). Současné poznatky o radikálové a kondenzační modifikaci polypropylenu byly shrnuty v teoretické části, kde je popsáno i využití reaktivně modifikovaného polypropylenu. Modifikace polypropylenu byla provedena radikálovým roubováním a následnou kondenzační reakcí amino sloučenin s naroubovaným anhydridem. Příprava radikálově roubovaného polypropylenu (PP-g-IAH) byla prováděna v souběžně rotujícím dvoušnekovém extruderu Brabender (25 DSE L/D = 34) při teplotě 230 °C, otáčkách 30 RPM a reakční době 3 minuty. Hmotnostní obsah monomeru v připraveném polymeru byl 0,5 hm %. Iniciátorem reakce byl peroxid 2,5 dimethy-2,5-bis(tert-butylperoxy) hexan (Luperox 101) v molárním poměru iniciátor/monomer = 1:0,6. Následně byl PP-g-IAH modifikován aminy v molárním poměru anhydrid/amin od 1:0,3 do 1:1 v jednošnekovém extruderu Betol (1825 L/D = 39). Reaktivní extruze probíhala při teplotě 210 °C, otáčky byly 30 RPM po dobu 3 minut. Analýzou vzorků pomocí infračervené spektroskopie byla stanovena konverze roubovací a kondenzační reakce a vliv amino sloučenin na vznik amidu a imidu anhydridu. Vliv přídavku amino sloučenin na krystalinitu polymeru byl analyzován pomocí diferenciální skenovací kalorimetrie. Termická stabilita modifikovaných polymerů byla studována pomocí termogravimetrické analýzy. Reologické chování modifikovaného PP bylo analyzováno měřením komplexní viskozity.
|
|
|
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.
|
|
|
Testování zpracovatelské stability polypropylenu roubovaného IAH
Hampapa, Břetislav ; Tocháček, Jiří (oponent) ; Kučera, František (vedoucí práce)
Bakalářská práce se zabývá testováním zpracovatelské stability polypropylenu roubovaného IAH (PP-g-IA). V teoretické části byly shrnuty dosud známé poznatky ohledně termické degradace derivátů kyseliny itakonové a polypropylenu (PP). V experimentální části byly vzorky připraveny z nemodifikovaného polypropylenu (PP) (Borsodchem, Maďarsko) a polypropylenu roubovaného anhydridem kyseliny itakonové (PP-g-IA), opakovanou degradací polymeru v extrudéru. Teplota trysky extrudéru byla 230 °C, otáčky 20 RPM, čas průchodu 4 min. Pomocí FT-IR spektroskopie byly sledovány funkční skupiny polymerů PP a PP-g-IA. Dále byl pozorován úbytek koncentrace naroubovaného itakonanhydridu v PP-g-IA. V závěru byly naměřeny hodnoty MVR podle normy ISO 1133, při teplotě 230 °C a závaží o hmotnosti 2,16 kg.
|
|
|
Functionalization of Poly(Lactic Acid)
Petruš, Josef ; Pospíšil, Ladislav (oponent) ; Alexy,, Pavol (oponent) ; Petrůj, Jaroslav (vedoucí práce)
The theoretical part of proposed thesis describes principle of radical grafting as well as the most important controlling factors affecting reaction course. Radical grafting of poly(lactic acid) (PLA) via reactive modification is the most promising technique for the preparation of biodegradable polymeric materials with various properties. Actual knowledge of PLA modification via radical grafting in melt is mentioned in the literature review as well as its potential applications. Experimental part deals with functionalization of PLA with itaconic anhydride (IAH) via radical grafting in the melt. Grafting reaction was initiated by 2,5-bis(tert-butylperoxy)-2,5-dimethylhexane (L101). In the first part, radical grafting is investigated “in situ” using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Exothermic peak on DSC thermogram reflects grafting reaction which allows calculation of activation energy of reaction. With regard to “in situ” TGA thermogram, formation of byproducts during radical modification was observed. In the second part, functionalization of PLA was achieved in discontinuous internal mixer under defined reaction conditions which were tailored to half-life time of chosen initiator and PLA processing parameters. Reaction temperature 190 °C was calculated according to Arrhenius equation and reaction time 6 min. These conditions were considered to be convenient with respect to decomposition kinetics of L101 and suppression of PLA degradation. IAH was succesfully grafted onto PLA backbone which was proved by Fourier transform infrared spectroscopy (FTIR) due to presence of –CH2 vibrations at 2860 and 2920 cm-1. Increase of integral intensity of the absorption band centered at 1750 cm-1 proved appearance of anhydride C=O vibrations overlapped by C=O vibrations of PLA backbone. Nuclear magnetic resonance (1H-NMR) did not detect oligomeric IAH grafted onto PLA. Different concentration of reactants (0.5–10 wt % of IAH, 0.1–2 wt % of L101) was applied in order to evaluate its influence on grafting yield and the extent of side reactions such as -scission, branching and crosslinking. At high concentration of both IAH and L101, IAH homopolymerization occurs although it is neglected in the most of research works. This argument is supported by colorimetric analysis, characterization of samples prepared by polymerization of IAH under grafting conditions and thermal stability of fractions extracted from PLA-g-IAH. Radical modification of PLA improves chain flexibility due to bulky IAH which was detected as a decrease of glass transition temperature (Tg). Increased content of amorphous phase, improved hydrophilicity, branched structure and chain scission enhanced biodegradability of PLA-g-IAH compared to neat PLA. Non-radical degradation during processing was proved by change of melt behaviour. This undesired effect was suppressed by addition of chain extender with reactive epoxy groups. Reaction between epoxy groups of chain extender and carboxyl groups of PLA was proved by structure analysis and change of rheological behavior of PLA-g-IAH.
|
|
|
Reaktivní zpracování polypropylénu
Matláková, Jana ; Žídek, Jan (oponent) ; Lehocký, Marián (oponent) ; Kučera, František (vedoucí práce)
Literární část popisuje princip radikálově iniciovaného roubování a vliv jednotlivých parametrů na průběh roubování. Rešerše shrnuje nejnovější poznatky v oblasti reaktivní modifikaci polypropylénu (PP), především je zaměřena na modifikaci PP pomocí anhydridů nenasycených kyselin. Teoretická část popisuje různé postupy a modifikace technologií za účelem zvýšení výtěžnosti roubování maleinanhydridu (MAH) na PP. Experimentální část je založena na pozorování vlivu koncentrace stabilizátorů, struktury peroxidů a kombinace monomerů na průběh a výtěžnost roubování PP. V první části byla stanovena kritická koncentrace stabilizátoru na základě experimentálně získané závislosti výtěžnosti roubování PP pomocí MAH na koncentraci stabilizátorů. Kinetické schéma roubování MAH na PP v přítomnosti stabilizátorů bylo navrženo a porovnáno s experimentálními výsledky. Vliv stabilizátorů na rozsah nežádoucího b-štěpení PP byl posouzen na základě indexu toku taveniny (MFR) a reologických křivek PP-g -MAH. V druhé části byl sledován vliv struktury peroxidu a koncentrace jednotlivých reaktantů na výtěžnost roubování MAH a anhydridu kyseliny itakonové (IAH) na PP. Počáteční rychlost roubování Rg byla experimentálně stanovena a následně porovnána s teoreticky vymezenou oblastí hodnot Rg. Rozsah b-štěpení PP byl výrazně ovlivněn strukturou a koncentrací peroxidu, jak ukázaly výsledky MFR a reologické křivky PP-g-MAH. Poslední část je zaměřena na posouzení kombinace MAH a IAH jako komonomerů na konverzi roubování. Nejprve byly roztokovou homopolymerací MAH, IAH a kopolymerací MAH a IAH připraveny referenční polymery. Referenční polymery byly analyzovány FTIR, DSC, WAXS za účelem potvrzení pravděpodobné kopolymerace MAH a IAH. Simulací blokové polymerace MAH, IAH a směsi MAH a IAH "in situ" v isotermickém kalorimetru byla sledována závislost reakční entalpie na čase. Následně byl modifikován PP kombinací MAH a IAH jako komonomerů za účelem posouzení vlivu na výtěžnost roubování.
|
|
|
Radikálové roubování PE/PP kopolymeru
Šido, Jiří ; Petrůj, Jaroslav (oponent) ; Kučera, František (vedoucí práce)
Diplomová práce se zabývá přípravou a charakterizací blokového kopolymeru PP/PE roubovaného anhydridem kyseliny itakonové v tavenině. Teoretická část se zabývá radikálově iniciovaným roubováním polárních monomerů na polyolefiny a využitím roubovaných polyolefinů. V experimentální části byly připraveny vzorky PP/PE roubovaného anhydridem kyseliny itakonové za různých podmínek roubování. Jako iniciátor byl použit 2,5-dimethyl- 2,5-bis(tert-buthylperoxy)hexan (LUPEROX 101). Roubování bylo prováděno v mixéru Brabender. Podmínky roubování byly: teplota 190-230°C, koncentrace monomeru 0,25 až 1 hm %, koncentrace iniciátoru 0,025-2 hm %, otáčky šneku 30 ot/min. Byl sledován vliv jednotlivých parametrů: koncentrace iniciátoru, koncentrace monomeru a teploty na konverzi monomeru, hodnotu MFI a rozsah homopolymerace monomeru. Přítomnost anhydridu navázaného na polymerním řetězci byla potvrzena FTIR spektroskopií. Kvalitativní stanovení obsahu navázaného anhydridu a konverze monomeru bylo prováděno alkalimetrickou titrací a potvrzeno FTIR spektroskopií.
|
|
|
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.
|
host ::
RSS.