Hydrolytic degradation of poly(ε-caprolactone) with different end groups and poly(ε-caprolactone-co--Y-butyrolactone): characterization and kinetics of hydrocortisone delivery

7 páginas, 8 figuras, 2 tablas.-- El pdf es el borrador del artículo.Asymmetric telechelic alfa-hydroxyl-ω-(carboxylic acid)-poly(ε-caprolactone) (HA-PCL), alfa-hydroxyl-ω-(benzylic ester)-poly(ε-caprolactone) (HBz-PCL), and an asymmetric telechelic copolymer alfa-hydroxyl-ω-(carboxylic acid)-poly(ε-caprolactone-co-Y-butyrolactone) (HA-PCB) were synthesized by ring-opening polymerization of ε-caprolactone (CL). CL and CL/-butyrolactone mixture were used to obtain homopolymers and copolymer respectively at 150°C and 2 hr using ammonium decamolybdate (NH4) [Mo10O34] (Dec) as a catalyst. Water (HA-PCL and HA-PCB) or benzyl alcohol (HBz-PCL) were used as initiators. The three polylactones reached initial molecular weights between 2000 and 3000 Da measured by proton nuclear magnetic resonance (1H-NMR). Compression-molded polylactone caplets were allowed to degrade in 0.5 M aqueous p-toluenesulfonic acid at 37°C and monitored up to 60 days for weight loss behavior. Data showed that the copolymer degraded faster than the PCL homopolymers, and that there was no difference in the weight loss behavior between HA-PCL and HBz-PCL. Caplets of the three polylactones containing 1% (w/w) hydrocortisone were placed in two different buffer systems, pH 5.0 with citrate buffer and pH 7.4 with phosphate buffer at 37°C, and monitored up to 50 days for their release behavior. The release profiles of hydrocortisone presented two stages. The introduction of a second monomer in the polymer chain significantly increased the release rate, the degradation rate for HA-PCB being faster than those for HBz-PCL and HA-PCL. At the pH studied, only slight differences on the liberation profiles were observed. SEM micrographs indicate that hydrolytic degradation occurred mainly by a surface erosion mechanism.The financial support by Consejo Nacional de Ciencia y Tecnología and Universidad de Guanajuato is acknowledged. L.M.O.C. thanks Consejo Nacional de Ciencia y Technología (CONACYT) for a Ph.D. scholarship.Peer reviewe

Functional, degradable polyester materials synthesized from poly(epsilon-caprolactone-co-2-oxepane-1,5-dione): An investigation into the derivatization, self assembly, and degradation behavior of poly(epsilon-caprolactone)-based materials

Biocompatible, degradable polymers possessing a high degree of complexity are an extremely desirable target for many applications. In order to further develop the range and utility of materials made from aliphatic polyesters, poly(epsilon-caprolactone-co-2-oxepane-1,5-dione) (P(CL-co-OPD)) was used as a polymeric precursor for the construction of a series of functional polyester-based materials. By taking advantage of the electrophilic ketone moieties characteristic of the OPD repeat unit, small molecule and polymer grafts were attached to the PCL backbone through the formation of both hydrazone and ketoxime ether linkages. This work has focused on both the synthesis and characterization of functional, degradable polyesters, including amphiphilic block graft copolymers, that possess significant potential for future use in diagnostic and therapeutic applications. A dansyl-functionalized poly(epsilon-caprolactone) was synthesized by reacting (P(CL-co-OPD) with dansyl hydrazine. The resulting dansylated-PCL displayed interesting fluorescence behavior and showed solvent polarity dependance as the fluorescence emission maxima shifted from 494 nm in toluene to 526 nm in dimethyl sulfoxide (DMSO). Analysis of the emission maximum of the dansyl-grafted polymer and a dansyl-functionalized small molecule analog with respect to three different solvent polarity parameters indicated that the fluorescence emission spectra of the dansylated polymer was influenced by solvent polarity, but that the dansyl fluorophore was overall less sensitive to the surrounding medium when grafted onto the polyester backbone. Degradable, amphiphilic graft copolymers of poly(epsilon-caprolactone)-graft-poly(ethylene oxide), PCL-g-PEO, were synthesized via a grafting onto strategy taking advantage of the ketones presented along the backbone of the statistical copolymer (PCL-co-OPD). Through the formation of stable ketoxime ether linkages, 3 kDa poly(ethylene oxide) (PEO) grafts and p-methoxybenzyl (pMeOBn) side chains were incorporated onto the polyester backbone with a high degree of fidelity and efficiency, as verified by NMR spectroscopy and GPC analysis (90% grafting efficiency in some cases). The resulting block graft copolymers displayed significant thermal differences, specifically a depression in the observed melting transition temperature, Tm, in comparison to the parent PCL and PEO polymers. These amphiphilic block graft copolymers underwent self assembly in aqueous solution with the P(CL-co-OPD-co-(OPD-g-PEO)) polymer forming globular micelles and a P(CL-co-OPD-co-(OPD-g-PEO)-co-(OPD-g-pMeOBn)) forming cylindrical or rod-like micelles, as observed by transmission electron microscopy (TEM) and atomic force microscopy (AFM). PCL-g-PEO copolymers synthesized from PCL-co-OPD that still contained free OPD units were found to undergo an early and rapid degradation upon being dispersed in aqueous solution. P(CL92-co-OPD5-co-(OPD-g-PEO)9) showed immediate signs of degradation upon being dispersed in aqueous solution based upon both 1H NMR spectroscopy and gel permeation chromatography (GPC) analysis. The solution state aggregates showed a minimal increase in aggregate size moving from a number-averaged hydrodynamic diameter (Dh) of 13 ± 3 nm at 0 h to 17 ± 3 nm at 24 h based upon analysis by dynamic light scattering (DLS). An increase in diameter upon degradation was corroborated by transmission electron microscopy (TEM) images showing circular particles that had a Dav of 15 ± 4 nm and 22 ± 5 nm at 0 and 24 h respectively. P(CL92-co-(OPD-g-PEO)8-co-(OPD-g-pMeOBn)6), a polyester having no free OPD units, showed no signs of rapid degradation over 24 h by 1H NMR or GPC analysis. Characterization of the solution state aggregates by DLS and TEM indicated that the circular particles formed by the PCL-g-PEO copolymer maintained both their size and morphology while being dispersed in aqueous solution for 24 h. P(CL327-co-OPD22-co-(OPD-g-PEO)15-co-(OPD-g-pMeOBn)8), a significantly larger PCL-PEO ketoxime ether conjugate possessing free OPD units, also showed signs of backbone degradation by 1H NMR and GPC upon being transitioned into aqueous solution. DLS analysis, of the solution state aggregates formed by this amphiphilic block graft copolymer showed no substantial changes in the hydrodynamic diameter over time. However, characterization by TEM showed a transition from circular to rod-like or cylindrical aggregates as hydrolysis occurred

Modification Of Pendant Anthracene And Azide Functionalized Polycarbonates Via Double Click Reactions

Tez (Yüksek Lisans) -- İstanbul Teknik Üniversitesi, Fen Bilimleri Enstitüsü, 2014Thesis (M.Sc.) -- İstanbul Technical University, Institute of Science and Technology, 2014Antrasen ve azid fonksiyonlu halkalı karbonat monomerleri sentezlenerek, ko-polimerizasyonu, benzil alkol başlatıcılığında, 1,8-diazabisiklo[5.4.0]undek-7-en ve 1-(3,5-bis(trifloromethil)fenil)-3-siklohekzil tiyoüre katalizörlüğündeki halka açılma polimerizasyonu ile gerçekleştirilmiştir.  Çalışmanın sonraki kısmında antrasen ve azid fonksiyonlu polikarbonat zincirine bakır katalizli azid-alkin siklokatılma (CuAAC) reaksiyonu ile Alkin-PCL ve Diels-Alder (DA) reaksiyonu ile maleimid uç fonksiyonlu PEG takılarak PC-g-PCL/PEG aşı kopolimeri elde edildi. Aşı kopolimerleri için Diels-Alder reaksiyon etkinliği UV-Vis spektroskopisi yardımıyla belirlendi. Elde edilen monomerler, öncü bileşikler, başlangıç polimerleri ve sonuç polimerler 1H NMR, UV, FT-IR ve GPC kullanılarak analiz edilmiştir.In this study, anthracene and azide functional cyclic carbonate monomers are synthesized, the co-polymerization of these was carried out successfully via ring-opening polymerization (ROP) using benzyl alcohol as initiator, 1,8-diazabicyclo[5.4.0]undec-7-ene and 1-(3,5-bis(trifluorometh1-(3,5-bis(trifluoromethyl))-3-cyclohexyl-2-thiourea, as catalyst system.  Subsequently, anthracene and azide functional polycarbonate chain, copper catalyzed azide-alkyne cycloaddition (CuAAC) by reaction of Alkyne-PCL, and Diels-Alder (DA) by reaction maleimide end-functionalized PEG attaching and  PC-g-PCL/PEG heterograft copolymer was obtained. Diels-Alder click reaction efficiency for graft copolymerization was monitored by UV-Vis spectroscopy. The structures of all monomers, initiators, polymer precursors and final polymers were confirmed exactly using GPC, 1H NMR, UV-Vis and FT-IR analyses.Yüksek LisansM.Sc

Functionalized crystalline polyactones as toughners for thermosetting resins

A crystalline polylactone is produced having reactive acrylate end groups. When incorporated into a thermosetting resin which includes reactive C.dbd.CH.sub.2 sites, the present functionalized polylactone acts as a toughener, greatly increasing the impact resistance of the final cured product. Also disclosed are carboxyl-bearing polylactones as tougheners for epoxy resin systems

Synthesis and characterisation of sequence-controlled multifunctional multiblock polyesters via quantitative one-pot iterative living ring-opening polymerisation (QOIL-ROP)

Scientists have devoted enormous efforts towards developing various synthetic strategies for translating the defined sequences and specific functions of natural biomacromolecules to the synthetic polymers. However, the majority of sequence-controlled polymers fabricated through existing synthetic strategies are commonly non-biodegradable and chain-transfer agents and the halides (used in metal-mediated approaches) are generally attached to the polymer backbone in many current liquid-phase iterative strategies even after isolation, which restrict their potential applications across a wide range of scientific and technological fields. Moreover, some existing synthetic strategies rely on thorough purifications in each cycle. Herein, this thesis presents the work on a novel and simple strategy for scalable production of well-defined sequence-controlled multifunctional multiblock polyesters composing biocompatible and biodegradable backbones with site-selective functionality via the new quantitative one-pot iterative living ring-opening polymerisation (QOIL-ROP) method. This new approach enables the synthesis of highly ordered multiblock copolyesters without any intermediate purification, allowing not only well-defined molecular weight but also nearly perfect unprecedented control of the microstructure in terms of the arbitrary distribution and chain length of each building block along the chain. To demonstrate the versatility of this approach, seven proof-of-concept polyesters were synthesised, including model quasi muliblock polyesters (A6A6A6A6A6 and A4A6A4A6A4) and multiblock copolyesters (A6B6A6B6A6, A4B6A4B6A4, A6B6A6A6B6, A6A6A6B6B6 and A6(B4C2)A6(B4C2)A6) with near-quantitative monomer conversions and relatively narrow molecular weight distributions for such complex structures in each cycle during the iterative polymerisation chain extension process. The sequence-controlled pentablock A6B6A6A6B6 copolyester was chosen to demonstrate scale-up synthesis on a multigram scale (∼56 g), further highlighting the robustness and commercialisation potential of the new strategy. This approach offers new perspectives for the design and synthesis of a new generation of artificial highly organised multifunctional macromolecular platform. Moreover, through this robust approach, prominently tunable physicochemical and biodegradable properties as well as structural and site-selective functional complexities were successfully built into the water-soluble, multifunctional, sequence-controlled polyesters by precisely controlling the chain composition, monomer sequence and chain length. This would unlock promising diverse, real-world applications from healthcare to nanotechnology and information storage.Open Acces

Полимеризация D,L-лактида в присутствии полиэфирполиола Boltorn™

Objects. To synthesize monodisperse biodegradable hyperbranched polymers based on D,L-lactide in the presence of Boltorn™ H30 polyester polyol as a macroinitiator.Methods. 1H and 13C nuclear magnetic resonance (NMR) spectroscopy was used to study the chemical structure of the Boltorn™ H30 polyester polyol and (Boltorn™ H30)-PDLA hyperbranched copolymers. The molecular weight distribution of the polymers was studied by gel permeation chromatography (GPC). In order to study the thermal stability of Boltorn™ H30 polyester polyol, thermogravimetric analysis (TGA) was used. Polymerization of D,L-lactide was carried out in a block in the presence of Boltorn™ H30 polyester polyol.Results. The degree of branching of Boltorn™ H30 polyester polyol was calculated from NMR data, while the TGA method was used to determine the upper operational temperature range. The polymerization of D,L-lactide in the presence of Boltorn™ H30 polyester polyol used as a macroinitiator was studied. The molecular weight characteristics of the obtained copolymers were studied by NMR and GPC.Conclusions. Optimum conditions were determined for the polymerization of D,L-lactide when using Boltorn™ H30 polyester polyol as a macroinitiator. The possibility of synthesizing narrowly dispersed hyperbranched polymers (Boltorn™ H30)-PDLA under the described conditions was demonstrated.Цели. Синтез узкодисперсных биоразлагаемых сверхразветвленных полимеров на основе D,L-лактида в присутствии полиэфирполиола Boltorn™ H30 в качестве макроинициатора.Методы. Для исследования химической структуры полиэфирполиола Boltorn™ H30 и сверхразветвленных сополимеров (Boltorn™ H30)-PDLA использовали 1H и 13С спектроскопию ядерного магнитного резонанса (ЯМР). Молекулярно-массовое распределение полимеров исследовали методом гель-проникающей хроматографии (ГПХ). Для исследования термической стабильности полиэфирполиола Boltorn™ H30 применяли метод термогравиметрического анализа (ТГА). Полимеризацию D,L-лактида в присутствии полиэфирполиола Boltorn™ H30 проводили в блоке.Результаты. По данным ЯМР была рассчитана степень разветвленности полиэфирполиола Boltorn™ H30. Методом ТГА определен верхний температурный диапазон работы с полиэфирполиолом Boltorn™ H30. Исследована полимеризация D,L-лактида в присутствии полиэфирполиола Boltorn™ H30 в качестве макроинициатора. Молекулярномассовые характеристики полученных сополимеров исследованы методами ЯМР и ГПХ.Выводы. Подобраны оптимальные условия полимеризации D,L-лактида в присутствии полиэфирполиола Boltorn™ H30 в качестве макроинициатора. Показана возможность синтеза узкодисперсных сверхразветвленных полимеров (Boltorn™ H30)-PDLA в этих условиях.