Biodegradable Aliphatic Polycarbonates Research Articles

Synthesis, thermal and barrier properties of biodegradable aliphatic polycarbonates with different chain lengths

Synthesis, thermal and barrier properties of biodegradable aliphatic polycarbonates with different chain lengths

Dual responsive self-healing hydrogels with wide stability and excellent mechanical strength based on aliphatic polycarbonate

The wide development of hydrogels had been used in many filed due to the high water-containing and tough three-dimensional structure, however, the poor mechanical and multi-functional properties of hydrogel can be limited in its applications deeply. Herein, the dual responsive self-healing hydrogels with tough mechanical properties were manufactured by dual-physical cross-linking based on biodegradable aliphatic polycarbonate. Choosing the soft and hard segments to design the polymeric hydrogel not only can facilitate the dual-dynamic bonding interactions but also the resilient hydrogels possess robust and controllable mechanical strength (6.51 MPa). Furthermore, the results of swelling and stability tests of the materials indicated that the swelling ability of the biodegradable hydrogels can be regulated by the hydrophilic group, and the maximal swelling ratio in water and the equilibrium water content is 66% and 40%, respectively. It is worth mentioning that the tough hydrogels embrace dual-responsive high efficiency of self-healing ability, and the self-healing time is 2 h at 50 °C or 10 h under pH = 5, suggesting that the obtained hydrogels can respond to temperature and pH value to drive the fracture interface for fast self-healing, which will offer new opportunities for stimuli-responsive materials and wound healing.

Investigating the Biodegradation Mechanism of Poly(trimethylene carbonate): Macrophage-Mediated Erosion by Secreting Lipase.

Poly(trimethylene carbonate) (PTMC), as one of the representatives of biodegradable aliphatic polycarbonates, has been found to degrade in vivo via surface erosion. This unique degradation behavior and the resulting nonacidic products make it more competitive with aliphatic polyesters (e.g., polylactide) in clinical practice. However, this surface degradation mechanism is complicated and not fully understood to date despite the findings that several reactive oxygen species and enzymes can specifically degrade PTMC in vitro. Herein, the biodegradation mechanism of PTMC was investigated by using possible degradation factors, distinct cell lines, and the inhibitors of these factors. The results demonstrate that PTMC undergoes a specific macrophage-mediated erosion. Macrophages tend to fuse into giant cells and elicit a typical inflammatory response by releasing proinflammatory cytokines. In addition, macrophages are suggested to primarily secrete enzymes (lipase specifically) to erode the PTMC bulk extracellularly as inhibiting their activity effectively prevented this eroding process. The clarification of the biodegradation mechanism in this work suggests that the degradation of PTMC highly depends on the foreign body response. Thus, it reminds the researchers to consider the effect of the microenvironment on the degradation and drug release of PTMC-based implantation devices and localized drug delivery systems.

Porous Hexacyanometallate(III) Complexes as Catalysts in the Ring-Opening Copolymerization of CO2 and Propylene Oxide

In this work, six porous hexacyanometallate complexes (Ni3[Co(CN)6]2, Co3[Co(CN)6]2, Fe3[Co(CN)6]2, Ni3[Fe(CN)6]2, Co3[Fe(CN)6]2, Fe4[Fe(CN)6]2) were synthesized by a complexing agent assisted coprecipitation method and thoroughly characterized via X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), in situ high-temperature X-ray diffraction (HT-XRD), elemental analysis (EA), X-ray fluorescence (XRF), scanning electron microscopy (SEM), transmission electron microscopy (TEM), N2 physisorption, and gas–solid phase titration with NH3. The thermal stability, chemical composition, pore size and volume, crystallite size and density of surface acid sites were strongly sensitive to both the transition metal and the cyanometallate anion employed. On that basis, transition metal hexacyanometallates must be perceived as an adaptable class of zeolite-like microporous materials. The catalytic properties of these compounds were tested by copolymerization of propylene oxide and CO2, a green route to obtain biodegradable aliphatic polycarbonates. All compounds under study showed moderate activity in the target reaction. The obtained copolymers were characterized by modest CO2 content (carbonate units ranging from 16 to 33%), random structure (RPEC ≈ 70%), and moderate molecular weight (Mw = 6000–85,400 g/mol) with broad dispersity values (ĐM = 4.1–15.8).

In Vivo Degradation Mechanism and Biocompatibility of a Biodegradable Aliphatic Polycarbonate: Poly(Trimethylene Carbonate-co-5-Hydroxy Trimethylene Carbonate).

A recently developed viscous liquid aliphatic polycarbonate, poly(trimethylene carbonate-co-5-hydroxy trimethylene carbonate), has advantageous properties for the delivery of acid-sensitive drugs such as proteins and peptides. This copolymer degrades in vitro via an alkaline-catalyzed intramolecular cyclization reaction yielding oligo (trimethylene carbonate), glycerol, and carbon dioxide, but its in vivo degradation mechanisms are presently unknown. The in vivo degradation mechanism and tissue response to this copolymer were investigated following subcutaneous implantation in Wistar rats. The molecular weight and composition of the copolymer varied in the same manner following subcutaneous implantation as observed in vitro. These findings suggest that the copolymer also degraded in vivo principally via intramolecular cyclization. The tissue response in terms of the inflammatory zone cell density, fibrous capsule thickness, and macrophage response was intermediate to that of two clinically used biodegradable sutures, Vicryl and Monocryl, indicating that the copolymer can be considered biotolerable. Collectively, the data show that further development of this copolymer as a drug delivery material is warranted.

Stimuli-Responsive Aliphatic Polycarbonate Nanocarriers for Tumor-Targeted Drug Delivery.

Nanoparticles based on amphiphilic copolymers with tunable physicochemical properties can be used to encapsulate delicate pharmaceutics while at the same time improving their solubility, stability, pharmacokinetic properties, reducing immune surveillance, or achieving tumor-targeting ability. Those nanocarriers based on biodegradable aliphatic polycarbonates are a particularly promising platform for drug delivery due to flexibility in the design and synthesis of appropriate monomers and copolymers. Current studies in this field focus on the design and the synthesis of new effective carriers of hydrophobic drugs and their release in a controlled manner by exogenous or endogenous factors in tumor-specific regions. Reactive groups present in aliphatic carbonate copolymers, undergo a reaction under the action of a stimulus: e.g., acidic hydrolysis, oxidation, reduction, etc. leading to changes in the morphology of nanoparticles. This allows the release of the drug in a highly controlled manner and induces a desired therapeutic outcome without damaging healthy tissues. The presented review summarizes the current advances in chemistry and methods for designing stimuli-responsive nanocarriers based on aliphatic polycarbonates for controlled drug delivery.

Influence of aliphatic polycarbonate middle block on mechanical and microstructural behaviour of triblock copolymers based on poly(l‐lactide) and polycarbonate

AbstractThree different ABA‐type triblock copolymers each containing biodegradable aliphatic polycarbonate as the middle block and poly(l‐lactide) as the outer blocks were synthesized and the influence of the methylene chain length of the aliphatic polycarbonate middle block on various properties of the triblock copolymers was evaluated. Differential scanning calorimetry and wide‐angle X‐ray diffraction studies revealed that the incorporation of the outer blocks reduced the crystallinity of the middle aliphatic polycarbonate block. Variation of methylene chain length of the middle block led to a change in morphology from spherical to cylindrical as evidenced from atomic force microscopy studies. In addition, the mechanical properties of the block copolymers showed semi‐ductile to quasi‐brittle behaviour depending upon the composition of the middle block which was also confirmed using scanning electron microscopy. Dynamic mechanical analysis of the triblock copolymers indicated that storage modulus increased with a decrease in methylene chain length. © 2018 Society of Chemical Industry

Well-Defined Selenium-Containing Aliphatic Polycarbonates via Lipase-Catalyzed Ring-Opening Polymerization of Selenic Macrocyclic Carbonate Monomer.

The synthesis of well-defined, biodegradable selenium-containing polymers remains a formidable challenge in polymer chemistry. Herein, a selenic cyclic carbonate dimer monomer (MSe) was developed to generate well-defined, biodegradable aliphatic polycarbonates with selenide functionality on the backbone. The monomer was synthesized via the intermolecular cyclization of di(1-hydroxyethylene) selenide and diphenyl carbonate with lipase CA as catalysts in a mass of anhydrous toluene with very dilute monomer concentration. Then living ring-opening polymerization (ROP) was executed by solution method using the same lipase CA as catalysts. Similarly, the copolymerizations with commercial trimethylene carbonate (TMC) generated random copolymers demonstrated by 13C NMR, regulating the density of selenium functional groups. The resulting polymers exhibited a living polymerization characteristic, as evidenced by polymerization kinetics, predictable molecular weights, narrow molecular-weight distribution, and controlled copolymer compositions. Using hydrophilic macroinitiators (PEG), amphiphilic di/triblock copolymers could be obtained, suggesting their potential as controlled drug delivery system (DDS) and hydrogel scaffolds for tissue engineering.

Biodegradable polycarbonates containing side carboxyl groups—synthesis, properties, and degradation study

ABSTRACTThe main objective of the presented research was to synthesise biodegradable aliphatic polycarbonates containing reactive carboxyl pendant groups and to examine the influence of the copolymer chain microstructure and composition on the process of their hydrolytic degradation and cytocompatibility. The work describes copolymerization of cyclic trimethylene carbonate derivative containing benzyl‐ester pendant group (benzyl 5‐methyl‐2‐oxo‐1,3‐dioxane‐5‐carboxylate) with trimethylene carbonate. The copolymerization was conducted with the use of zinc (II) and lanthanum (III) acetylacetonates as ring‐opening polymerization coordination initiators. Detailed NMR analysis allowed to define the microstructure of the obtained copolymers, which depended on the composition and type of used initiator. The final tapered chain microstructure of the obtained copolymers was related to huge differences in comonomers reactivity and evidenced low level of transesterification of the main copolymer backbone. Chosen copolymers, with unprotected carbonyl groups, were subjected to in vitro degradation test and cytocompatibility studies. It was found that high concentration of carboxyl groups resulted in copolymers which formed hydrogels and were very prone to hydrolytic degradation; they were also cytotoxic toward osteoblast‐like MG 63 cells. Copolymers with lower content of carboxyl groups were found less susceptible to degradation and cytocompatible with studied cells. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 2756–2769

"Brill Transition" Shown by Green Material Poly(octamethylene carbonate).

Poly(octamethylene carbonate) (POMC), as the eighth member of the newly developed biodegradable aliphatic polycarbonate family, demonstrates a reversible crystal-crystal transition, which is highly similar to Brill transition extensively studied in the nylon family. With the dipole-dipole interaction in POMC much weaker than the hydrogen bonding, POMC exhibits its "Brill transition" temperature at around 42 °C, much lower than nylons. The two crystalline structures of POMC at below and above the transition temperature can be identified. The transition of POMC is largely associated with the reversible conformation change of methylene sequences from trans-dominated at low temperatures to trans/gauche coexistence at high temperatures.

Improving the thermal and mechanical properties of poly(propylene carbonate) by incorporating functionalized graphite oxide

AbstractPoly(propylene carbonate) (PPC) is a new biodegradable aliphatic polycarbonate. However, the poor thermal stability, low glass transition temperatures (Tg), and relatively low mechanical property have limited its applications. To improve the thermal and mechanical properties of PPC, functionalized graphite oxide (MGO) was synthesized and mixed with PPC by a solution intercalation method to produce MGO/PPC composites. A uniform structure of MGO/PPC composites was confirmed by X‐ray diffraction and scanning electron microscope. The thermal and mechanical properties of MGO/PPC composites were investigated by thermal gravimetric analysis, differential scanning calorimetric, dynamic mechanical analysis, and electronic tensile tester. Due to the nanometer‐sized dispersion of layered graphite in polymer matrix, MGO/PPC composites exhibit improved thermal and mechanical properties than pure PPC. When the MGO content is 3.0 wt %, the MGO/PPC composites shows the best thermal and mechanical properties. These results indicate that nanocomposition is an efficient and convenient method to improve the properties of PPC. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

Preparation and properties of poly(propylene carbonate maleate) microcapsules for controlled release of pazufloxacin mesilate

AbstractA novel biodegradable aliphatic polycarbonate, poly(propylene carbonate maleate) (PPCMA) was synthesized by terpolymerization of carbon dioxide, propylene oxide, and maleic anhydride (MA), using a polymer supported bimetallic complex as catalyst. The utility of PPCMA to encapsulate and control the release of drug pazufloxacin mesilate (PZFX), via microcapsules, was investigated. PPCMA microcapsules containing PZFX were elaborated by solvent evaporation method based on the formation of double W/O/W emulsion. The manufacturing parameters such as the volume ratio of V(PPCMA) : V(PZFX), the concentration of stabilizer gelatin in outer aqueous phase played major roles on microcapsule characters, and were altered to optimize the process parameters. The PPCMA‐PZFX microcapsules were obtained with smooth and spherical surface under optimum condition, the mean diameter of microcapsules was ∼ 2 μm, and the drug loading and drug encapsulation efficiency of the microcapsules were 22.9 ± 1.05% and 82.1 ± 2.03%, respectively. PZFX released from PPCMA microcapsules was found to reach 89.8 ± 2.89% after 36d in a pH 7.4 phosphate‐buffered solution, and the release profile obeyed the Higuchi equation. The results suggest that the new polymer PPCMA provides an alternative to degradable matrix polymers for long‐term sustained releasing drug delivery systems. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

Preparation and Characterization of Poly(propylene carbonate)/Alkali Lignin Composite Sheets by Calendering Process

PPC is a new biodegradable aliphatic polycarbonate with poor thermal stability and mechanical properties which is difficult to form sheets or films and so on. Through the addition of alkali lignin, thermal stability and mechanical properties of PPC was improved largely. PPC/ alkali lignin sheets could be prepared. DSC results showed that the thermal stability of PPC was improved by the introduction of alkali lignin. SEM showed good dispersion of alkali lignin particles into PPC matrix that resulted in good miscibility. Improved mechanical properties and thermal stability of PPC/ alkali lignin blends were attributed to stronger interfacial interaction of PPC and alkali lignin. These results indicate that blending PPC with alkali lignin is an efficient and convenient method to improve the properties of PPC.

Preparation and characterization of poly(propylene carbonate)/polystyrene composite films by melt-extrusion method

AbstractPoly(propylene carbonate) (PPC) is a new biodegradable aliphatic polycarbonate with poor thermal stability and mechanical properties which shows difficulty in forming film by melt-extrusion technology. Through the addition of polystyrene (PS), the melt-extrusion film processability, thermal stability and mechanical properties of PPC was improved largely. PPC/PS films were prepared in the the melt-extrusion process successfully. DSC data showed that there was some degree of miscibility between PPC and PS. SEM showed good dispersion of PS particles into PPC matrix. Improved mechanical properties and thermal stability of PPC/PS blends were attributed to homogeneous dispersing and stronger interfacial interaction of PS and PPC. These results indicate that blending PPC with PS is an efficient and convenient method to improve the properties of PPC, and the composites can be used as a common packaging material for a wide range of applications.

NOVOZYM-435 CATALYZED RING-OPENING POLYMERIZATION OF A MACROCYCLIC CARBONATE

Biodegradable aliphatic polycarbonates have attracted great attentions as an important kind of biomedical materials.In this study metal-free ring-opening polymerization of 14-membered dimmer,cyclobis(tetramethylene carbonate)[(TeMC)_2] was attempted at 75℃ in toluene and in the presence of porcine pancreas lipase(PPL),candida rugosa lipase(Lipase AYS)or immobilized lipase Novozyme-435 to afford poly(tetramethylene carbonate).It was found that Novozyme-435 exhibited comparatively high catalytic activity with Sn(Oct)_2 while PPL and AYS exhibited no obvious activity to the polymerization of(TeMC)_2 with respect to the conversion and molecular weight.Optimal reaction conditions including monomer concentration and Novozyme-435 concentration were explored in an effort to positively influence the outcome of the ring-opening polymerization.The polymerization rate was markedly increased with increasing the enzyme concentration.A region exists around toluene/(TeMC)_2(mL/g)ratio of 4∶1 where Novozyme-435-catalyzed polymerizations could result in higher molecular weight and monomer conversion.It is interesting to point out that in the absence of toluene,the solid-phase polymerization could also occur at predetermined temperature of 75℃,which was much lower than the melting point of(TeMC)_2(T_m=170～172℃).The result of kinetic studies of polymerization showed that Novozym-435-catalyzed polymerization of(TeMC)_2 did not behave living characteristics reported for that of e-caprolactone.The experimental data also indicated that the immobilized lipase Novozyme-435 could be repeatedly used with high activity.

Preparation and characterization of poly(propylene carbonate)/montmorillonite nanocomposites by solution intercalation

Poly(propylene carbonate) (PPC) is a new biodegradable aliphatic polycarbonate. However, the poor thermal stability and low glass transition temperatures ( T g) have limited its applications. To improve the thermal properties of PPC, organophilic montmorillonite (OMMT) was mixed with PPC by a solution intercalation method to produce nanocomposites. An intercalated-and-flocculated structure of PPC/OMMT nanocomposites was confirmed by X-ray diffraction (XRD) and transmission electron microscopy (TEM). The thermal and mechanical properties of PPC/OMMT nanocomposites were investigated by thermal gravimetric analysis (TGA), differential scanning calorimetric (DSC), and electronic tensile tester. Due to the nanometer-sized dispersion of layered silicate in polymer matrix, PPC/OMMT nanocomposites exhibit improved thermal and mechanical properties than pure PPC. When the OMMT content is 4 wt%, the PPC/OMMT nanocomposite shows the best thermal and mechanical properties. These results indicate that nanocomposition is an efficient and convenient method to improve the properties of PPC.

Biodegradable Polycarbonate Synthesis by Copolymerization of Carbon Dioxide with Epoxides Using a Heterogeneous Zinc Complex

AbstractAs a means for the chemical fixation of carbon dioxide and the synthesis of biodegradable polycarbonates, copolymerizations of carbon dioxide with various epoxides such as cyclohexene oxide (CHO), cyclopetene oxide, 4‐vinyl‐1‐cyclohexene‐1,2epoxide, phenyl glycidyl ether, allyl glycidyl ether, propylene oxide, butene oxide, hexene oxide, octene oxide, and 1‐chloro‐2,3‐epoxypropane were investigated in the presence of a double metal cyanide catalyst (DMC). The DMC catalyst was prepared by reacting K3Co(CN)6 with ZnCl2, together with tertiary butyl alcohol and poly(tetramethylene ether glycol) as complexing reagents and was characterized by various spectroscopic methods. The DMC catalyst showed high activity (526.2 g‐polymer/g‐Zn atom) for CHO/CO2 (PCO2 = 140 psi) copolymerization at 80 °C, to yield biodegradable aliphatic polycarbonates of narrow polydispersity (Mw/Mn = 1.67) and moderate molecular weight (Mn = 8900). The DMC catalyst also showed high activities with different CO2 reactivities for other epoxides to yield various aliphatic polycarbonates with narrow polydispersity.

Thermal properties and rheological behavior of biodegradable aliphatic polycarbonate derived from carbon dioxide and propylene oxide

AbstractAlternating poly(propylene carbonate)s (PPCs) were synthesized from carbon dioxide and propylene oxide on a relatively larger scale. The thermal properties of the alternating PPC copolymers, with various molecular weights, were investigated with modulated differential scanning calorimetry (MDSC) and thermogravimetric analysis (TGA). The melt‐flow indices of the as‐made PPCs were determined in a melt‐flow indexer, and the rheological properties of the PPCs were studied with a capillary rheometer. The MDSC and TGA results showed that the glass‐transition temperatures of the PPCs increased with increasing molecular weight. The rheological measurements revealed that the PPCs exhibited pseudoplastic flow behavior in the melt. The molecular weight played a key role in the rheological behavior of the PPCs. Moreover, the PPCs with high molecular weights were more sensitive to the temperature and shear rate than those with low molecular weights. The melt viscosity of the PPCs with low molecular weights decreased dramatically with increasing temperature. The flow activation energy of such PPCs diminished with an increase in the shear rate, whereas the flow activation energy of the PPCs with high molecular weights remained nearly unchanged. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 711–716, 2004

Novel Biodegradable Aliphatic Polycarbonate Based on Ketal Protected Dihydroxyacetone

AbstractSummary: A novel aliphatic polycarbonate based on ketal protected dihydroxyacetone was synthesized by ring‐opening polymerization of cyclic carbonate monomer, 2,2‐ethylenedioxypropane‐1,3‐diol carbonate (EOPDC), in bulk. Effects of polymerization conditions such as catalysts, catalyst concentration, reaction temperature and reaction time on the polymerization were investigated. The polycarbonate obtained was characterized by GPC, FTIR, 1H NMR, 13C NMR and DSC. The study on in vitro degradation of PEOPDC shows that the degradation mainly results from surface erosion.Synthesis of an aliphatic polycarbonate with a high molecular weight by ring‐opening polymerization of cyclic carbonate monomer EOPDC.imageSynthesis of an aliphatic polycarbonate with a high molecular weight by ring‐opening polymerization of cyclic carbonate monomer EOPDC.

Melt processable and biodegradable aliphatic polycarbonate derived from carbon dioxide and propylene oxide

AbstractAlternating poly(propylene carbonate)s (PPC)s were successfully synthesized from carbon dioxide and propylene oxide in higher yield than previously reported. Such thermally stable and high molecular weight copolymers were achieved by optimizing the reaction conditions. The molecular structural change and mechanical properties of the alternating copolymer subjected to melt extrusion were examined by means of modulated differential scanning calorimetry (MDSC), thermogravimetric analysis (TGA), NMR, and tensile tests. The MDSC and TGA results showed that the alternating copolymer generally exhibits a high glass‐transition temperature of above 40°C and a decomposition temperature of above 250°C. These PPCs can be readily melt processed under conditions similar to those for commercial polyolefins. For instance, they can be melt extruded in a temperature range from 150 to 170°C under varying extrusion pressures. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3301–3308, 2003