Synthesis and characterization of biodegradable homopolymers and block copolymers based on adipic anhydride

Homopolymers of adipic anhydride (AA) and block copolymers of ϵ-caprolactone (ϵ-CL) and AA have been synthesized with aluminum triisopropoxide as an initiator. Homopolymerization was studied at 20°C in toluene and methylene chloride (CH₂Cl₂). The end-group analysis agrees with a coordination insertion mechanism based on the acyl-oxygen cleavage of the AA ring. Living poly(ϵ-caprolactone) (PCL) chains are very efficient macro-initiators for the polymerization of AA, with formation of diblock copolymers of a narrow molecular weight distribution. At our best knowledge, low molecular weight ω-aluminum alkoxide PCL macroinitiators (M_n < 1000) allow the first valuable synthesis of PAA with a molecular weight as high as 58,000 and a quite narrow polydispersity (M_w/M_n = 1.2). Size-exclusion chromatography (SEC) and ¹³C NMR confirm the blocky structure of the copolymers, in agreement with DSC that shows two melting endotherms and two glass transitions characteristic of the crystalline and amorphous phases of PCL and PAA, respectively. Block copolymers of ϵ-CL and AA are also sensitive to hydrolysis, which makes them possible candidates for biomedical applications. Initiation of the AA polymerization in bulk with aluminum triisopropoxide in the presence of various ligands is also discussed. © 1997 John Wiley & Sons, Inc.     

Photo-crosslinking copolymers based polyanhydride and 1G polyamidoamine-methacrylamide as bone tissue engineering: Synthesis, characterization, and in vitro degradation

In the past decade, Biodegradable materials that are capable of in situ formation have attracted increased attention for use in restorative orthopedic devices. In this communication, the surface erosion biodegradable polymers derived from 1.0G-polyamidoamine-double bond (PAMAM-DB) and methacrylated sebacic anhydrides (MSA) were evaluated over 2 months period under physiological conditions. Rectangular shaped samples were prepared by crosslinking the components using both chemical and photo initiators and exposure to UV light. The effects of PAMAM-DB: MSA ratio on local pH, water uptake, mass loss, and mechanical properties were explored. Polymers were characterized by ¹H NMR, ¹³C NMR, FT-IR, compressive strength testing and SEM. It is found that copolymer with 50-60% PAMAM-DB (mass fraction) show more excellent mechanical properties compared with other formulations. Copolymers degraded mainly by surface erosion but the bulk erosion pattern also appeared at the initial time of degradation for formulation 30% and 40%. The material was expected to be useful for drug controlled delivery, tissue engineering scaffold and other biomedical applications.     

Synthesis,characterization, and enzymatic degradation of network aliphatic copolyesters

Network copolyesters were prepared from glycerol (Yg) and sebacic acid (10) with 10–90 mol % of either succinic acid (4), 1,12-dodecanedicarboxylic acid (14), 1,18-octadecanedicarboxylic acid (20), or terephthalic acid (T). Prepolymers prepared by melt-polycondensation were cast from dimethylformamide solution and postpolymerized at 230–250°C for various periods of time to form a network. The resultant films were transparent, flexible, and insoluble in organic solvents. The network copolyesters obtained were characterized by infrared absorption spectra, wide angle X-ray diffraction analysis, density measurement, thermomechanical analysis, differential scanning calorimetry, and tensile test. The enzymatic degradation was estimated by weight loss of the network copolyester films in a buffer solution with Rhizopus delemar lipase at 37°C. The weight loss due to the enzymatic degradation was decreased with increasing comonomer content, and the copolyesters with Yg4, Yg20 and YgT more than 50 mol % were not degraded by lipase enzyme at all. On the contrary, Yg-10/14 films were degraded appreciably over whole range of comonomer composition. With increasing comonomer content, the heat distortion temperature increased gradually, while the tensile strength and Young's modulus were not changed much. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 2005–2011, 1999     

Degradable polymer networks and star polymers based on mixtures of two cleavable dimethacrylate crosslinkers: Synthesis,characterization, and degradation

Mixtures of two cleavable dimethacrylate crosslinkers, the hydrolyzable di(methacryloyloxy‐1‐ethoxy)methane (DMOEM) and the thermolyzable 1,1‐ethylenediol dimethacrylate (EDDMA), were used for the preparation of neat crosslinker polymer networks, randomly crosslinked polymer networks of methyl methacrylate (MMA), and star polymers of MMA, using group transfer polymerization in tetrahydrofuran (THF). All star polymers and randomly crosslinked polymer networks containing mixtures of the hydrolyzable DMOEM and the thermolyzable EDDMA crosslinkers gave THF‐soluble final products when subjected to sequential thermolysis and hydrolysis, in this order. When applying sequential hydrolysis and thermolysis, only the star polymers with an EDDMA crosslinker content equal to or higher than 50% gave THF‐soluble final products. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 5853–5870, 2009     

Synthesis, characterization and degradation of well-defined crosslinkable aliphatic polyesters end-capped by biomesogenic units

Novel biodegradable-cum-crosslinkable polyesters end-capped by biomesogenic units, cinnamic acid (CA) and ferulic acid (FA), were synthesized via chain-growth polycondensation in solid-liquid phase. The chemical structure of synthesized polymers was characterized by Fourier transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance spectroscopy (¹H NMR). The composition of polyesters, which was calculated by ¹H NMR, was in agreement with the feed ratios. The thermal properties and crystallinity of polyesters were measured by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), wide angle X-ray diffraction (WXRD) and polarizing-light microscopy (PLM). It was found that the polyesters possessed good crystallinity. Furthermore, the obtained polyesters could be crosslinked with methyl methacrylate (MMA), n-butyl acrylate (BA) and styrene (St) under thermal condition. The crosslinked products possessed degradability in phosphate buffer solution at 37 °C, which might be potentially applied as biomaterials.     

Synthesis of degradable molecular brushes via a combination of ring-opening polymerization and click chemistry

Acid-degradable molecular brushes with polycarbonate backbone and densely grafted side chains (∼1.9 SCs per backbone repeating unit) were synthesized for the first time using the grafting-onto method. Extremely efficient copper-catalyzed azide-alkyne cycloaddition click reactions between the polycarbonate backbone containing two pendant azido groups per backbone unit and alkynyl-terminated poly (methyl acrylate) (ay-PMA₇₂, average degree of polymerization DP = 72) SCs were demonstrated to finish in 10 min with a quantitative conversion of the azido groups. Similar grafting efficiencies were also achieved when using alkynyl-terminated polystyrene (ay-PS), poly(ethylene oxide) (ay-PEO), and poly (t-butyl acrylate)-b-polystyrene (ay-PtBA-b-PS) to successfully prepare molecular brushes with high grafting density (>1.8 SCs per backbone repeating unit). Under acidic condition, the polycarbonate backbones were completely degradable and the final degraded product of the molecular brushes was a linear polymer chain with molecular weight two times of the SCs. When a mixture of hydrophobic ay-PS and hydrophilic ay-PEO chains was used, amphiphilic heterobrushes PC-g-(PS-co-PEO) were synthesized, which could self-assemble into micelles or vesicles in selective solvents, depending on the ratio of the two SCs in the brush. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 239–248     

Synthesis, characterization and in vitro degradation study of a novel and rapidly degradable elastomer

Biodegradable elastomers represent a useful class of biomaterials. In this paper, a novel biodegradable elastomer, poly(PEG-co-CA) (PEC), was synthesized by condensation of poly(ethylene glycol) (PEG) and citric acid (CA) under atmospheric pressure without any catalyst. We first synthesized a pre-polymer by carrying out a controlled condensation reaction between PEG and citric acid, and then post-polymerised and simultaneously cross-linked the pre-polymer in the mould at 120 °C. The pre-polymer was characterized by FT-IR, ¹H NMR, ¹³C NMR, GPC and DSC. A series of polymers were prepared at different post-polymerisation time and different monomer ratios. Measurements on the mechanical properties of PEC testified that the new polymers are elastomers with low hardness and big elongation, and hydrolytic degradation of the polymer films in a buffer of pH 7.4 at 37 °C showed that PEC had excellent degradability (all the films show the weight losses more than 60% after 96 h incubation). The different post-polymerisation time and monomer ratio had strong influence on the degradation rates and mechanical performances. The material is expected to be useful for controlled drug delivery and other biomedical applications.     

Thermolyzable polymer networks and star polymers containing a novel,compact, degradable acylal‐based dimethacrylate cross‐linker: Synthesis,characterization, and thermolysis

A compact, cleavable acylal dimethacrylate cross‐linker, 1,1‐ethylenediol dimethacrylate (EDDMA), was synthesized from the anhydrous iron(III) chloride‐catalyzed reaction between methacrylic anhydride and acetaldehyde. The ability of EDDMA to act as cross‐linker was demonstrated by using it for the preparation of one neat cross‐linker network, four star polymers of methyl methacrylate (MMA), and four randomly cross‐linked MMA polymer networks using group transfer polymerization (GTP). For comparison, the corresponding polymer structures based on the commercially available ethylene glycol dimethacrylate (EGDMA) cross‐linker (isomer of EDDMA) were also prepared via GTP. The number of arms of the EDDMA‐based star polymers was lower than that of the corresponding EGDMA polymers, whereas the degrees of swelling in tetrahydrofuran of the EDDMA‐based MMA networks were higher than those of their EGDMA‐based counterparts. Although none of the EDDMA‐containing polymers could be cleanly hydrolyzed under basic or acidic conditions, they could be thermolyzed at 200 °C within 1 day giving lower molecular weight products. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5811–5823, 2007     

Phenolic materials via ring-opening polymerization: Synthesis and characterization of bisphenol-A based benzoxazines and their polymers

Compounds with bifunctional benzoxazine groups in their molecular structures form crosslinked structures characteristic of phenolic materials through a ring-opening reaction mechanism. This family of compounds offers greater flexibility than conventional novolac or resole resins in terms of molecular design. It is also superior to conventional phenolic resin in process control since it releases no by-product during curing reactions. The materials thus obtained exhibit excellent mechanical integrity with glass transition temperatures over 200°C. The synthesis, composition, and structural analysis of precursors based on bisphenol-A are discussed herein. © 1994 John Wiley & Sons, Inc.     

Synthesis, characterization and in vitro degradation of a novel degradable poly((1,2-propanediol-sebacate)-citrate) bioelastomer

Degradable bioelastomers represent a useful class of biomaterials. In this paper, a novel biodegradable network of elastomeric polyesters, poly((1,2-propanediol-sebacate)-citrate) (PPSC), was synthesized by condensation of 1,2-propanediol, sebacic acid and citric acid without any catalyst. An oligomeric diol of 1,2-propanediol-sebacate was first synthesized by carrying out a controlled condensation reaction between 1,2-propanediol and sebacic acid, and then a pre-polymer was synthesized by condensation of the diol and citric acid, whereat the pre-polymer was post-polymerized and simultaneously crosslinked in mold at 120 °C. A series of PPSC polymers were prepared at different post-polymerization times and different monomers' ratio. T_g confirms that PPSC is totally amorphous at 37 °C. The mechanical properties of PPSC testified that the new polymers are typical elastomers with low hardness and large elongation. The different post-polymerization times and monomers' ratio had strong influence on the degradation rates and mechanical performances. The material was expected to be useful for drug controlled delivery, tissue engineering scaffold and other biomedical applications.     

Synthesis and characterization of ABA-type block copolymer of poly(trimethylene carbonate) with poly(ethylene glycol): Bioerodible copolymer

ABA-type block copolymers of poly(trimethylene carbonate) with poly(ethylene glycol) (M_n 6820), PTMC-b-PEG-b-PTMC, were synthesized by the ring-opening polymerization of 1,3-dioxan-2-one (trimethylene carbonate) in the presence of poly-(ethylene glycol) with stannous octoate catalyst, and the copolymers with various compositions were obtained. The PTMC-b-PEG-b-PTMC copolymers were characterized with Fourier transform infrared and nuclear magnetic resonance spectroscopies. The intrinsic viscosities of resulting copolymers increased with the increase of 1,3-dioxan-2-one content in feed while the molar ratio of monomer over catalyst kept constant. It has been observed that the glass transition temperature (T_g) of the PTMC segments in copolymers, recorded from differential scanning calorimetry, was dependent on the composition of copolymers. The melting temperature (T_m) of PEG blocks in copolymer was lower than that of PEG polymer, and then disappeared as the length of PTMC blocks increased. The results of dynamic contact angle measurement clearly revealed that the hydrophilicity of resulting copolymers increased greatly with the increase of PEG content in copolymers. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 695–702, 1998     

Fast degradable poly(L‐lactide‐co‐ε‐caprolactone) microspheres for tissue engineering: Synthesis,characterization, and degradation behavior

Polymeric scaffolds play a crucial role in engineering process of new tissues and effect the cell growth and viability. PLCL copolymers are found to be very useful during cell growth due to their elastic behavior and mechanical strength. Thus, low molecular weight PLCL copolymers of various ratios viz. PLCL(90/10), PLCL(75/25), PLCL(50/50) and PCL were synthesized by ring opening polymerization using stannous octoate as a catalyst. Synthesized polymers were characterized by GPC, ¹H‐NMR, FTIR and XRD. The thermal properties of the copolymers were studied using TGA and DSC. Microspheres of about 100 μm diameter were prepared for different copolymers and their in vitro degradation behaviors were studied up to 108 days. It was observed that degradation of PLA content in polymer backbone occurs faster than PCL component which is also indicated by corresponding change in ratios of PLA/PCL, as determined by ¹H‐NMR. SEM images of microspheres depicted the surface morphology during degradation and suggested the faster degradation for PLCL (50:50). Copolymers of different thermal, mechanical properties and different degradation behaviors can be prepared by adjusting the composition of copolymers. Various synthesized polymers from this work have been tested in our laboratory as polymeric scaffold for soft tissue engineering. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 2755–2764, 2007     

Synthesis and characterization of degradable hyperbranched poly(2‐ethyl‐2‐oxazoline)

Hyperbranched poly(2‐ethyl‐2‐oxazoline) was synthesized by a combination of cationic ring‐opening polymerization and the oxidation of thiol to disulfide groups. A three‐arm star poly(2‐ethyl‐2‐oxazoline) (PEtOx) was first synthesized using 1,3,5‐tris(bromomethyl) benzene as an initiator. The star PEtOx was end‐capped with potassium ethyl xanthate. Similarly, a linear PEtOx was synthesized and end‐capped with potassium ethyl xanthate using benzyl bromide as an initiator. Hyperbranched PEtOx was then obtained by in situ cleaving and subsequent oxidation of the star PEtOx and linear PEtOx mixture with n‐butylamine as both a cleaving agent and a base in tetrahydrofuran. The linear PEtOx was used to prevent the formation of gel. The hyperbranched PEtOx can be cleaved with dithiothreitol to trithiol and monothiol polymer. The hyperbranched PEtOx shows no remaining thiols using Ellman's assay. The resulting hyperbranched PEtOx was hydrolyzed to a novel hyperbranched polyethyleneimine with degradable disulfide linkages. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2030–2037     

Biodegradable liquid crystalline aromatic/aliphatic copolyesters. Part I: Synthesis, characterization, and hydrolytic degradation of poly(butylene succinate-co-butylene terephthaloyldioxy dibenzoates)

To increase the thermal and mechanical properties of the aliphatic polyester poly(butylene succinate) (PBS), a series of potentially biodegradable liquid crystalline aromatic/aliphatic random copolyesters were prepared by melt polycondensation of new mesogenic monomers dimethyl 4,4′-(terephthaloyldioxy) dibenzoate (MTB), dimethyl succinate, and 1,4-butanediol. The synthesized copolyesters were characterized by means of proton nuclear magnetic resonance spectroscopy (¹H NMR), gel permeation chromatography (GPC), viscosity measurements, differential scanning calorimetry (DSC), thermogravimetry (TG), X-ray diffraction (XRD), polarizing light microscopy (PLM) and mechanical property measurements. The MTB content was varied so that the effects of the mesogen content on the thermal and mechanical properties, degradable behaviours and mesophase were examined. It was found that introducing the rigid rod mesogens could increase the thermal stability and the mechanical properties, while it reduced the melting temperature (T_m), the crystallization temperature (T_c), the degree of relative crystallinity (X_c) and the hydrolytic degradation rate. Only the homopolyester poly(butylenes terephthaloyldioxy dibenzoates) was able to show the schlieren texture characteristic of nematics.     

Enzymatic‐ and light‐degradable hybrid nanogels: Crosslinking of polyacrylamide with acrylate‐functionalized Dextrans containing photocleavable linkers

Enzymatically cleavable and light‐degradable hybrid nanogels were prepared by free radical inverse miniemulsion copolymerization of acrylamide (AAm) with a newly synthesized functional dextran crosslinker containing acrylate moieties attached to the backbone via a photolabile linker, that is, dextran‐photolabile linker‐acrylate (Dex‐PL‐A). The Dex‐PL‐A/AAm feed ratio was systematically varied to investigate the influence of the particle composition on the gel properties. The resulting hydrogel nanoparticles were examined with regard to their degradation behavior upon the appliance of the two orthogonal stimuli by turbidity measurements in combination with dynamic light scattering. Although continuous photolytic cleavage of the photolabile linkers between polyacrylamide chains and dextran molecules was found to proceed fast and quantitatively yielding completely disintegrated networks, stepwise irradiation resulted in partial degradation of crosslinking points. Thus, nanogels of a desired specific degree of swelling (DGS) can be obtained by adjusting the irradiation time accordingly. Partial enzymatic cleavage of the dextran backbones of the Dex‐PL‐A crosslinking molecules resulted in an increase in the DGS of the nanogels up to a constant value. Subsequent irradiation of those swollen hydrogel particles was used to fully degrade the network structure in a second step. Hence, a two‐step degradation profile was realized by the combination of the two orthogonal stimuli. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Facile synthesis and characterization of Fe2O3 nanoparticles using L-lysine and L-serine for efficient photocatalytic degradation of methylene blue dye

In this work, Fe₂O₃ nanoparticles, abbreviated as OL and OS, were facilely synthesized by the combustion procedure using L-lysine and L-serine as organic fuels, respectively. Also, the OL and OS samples were identified using different instruments such as Raman spectrometer, FT-IR spectrophotometer, UV–Vis spectrophotometer, XRD, HR-TEM, BET surface area, and FE-SEM. The XRD confirmed that the mean grain size of OL and OS samples is 42.23 and 33.16 nm, respectively. The HR-TEM images confirmed that irregular, hexagonal, and spherical shapes, have an average diameter of 39.13 and 34.28 nm, were observed in the OL and OS samples, respectively. The BET surface area of the OL and OS samples is 16.20 and 28.34 m²/g, respectively. Additionally, the OL and OS samples were accomplished for the photocatalytic degradation of methylene blue dye in the absence and presence of hydrogen peroxide. The % degradation of 45 mL of 25 mg/L of methylene blue dye in the case of using OL and OS samples in the absence of hydrogen peroxide is 55.23 and 63.64 % after 120 min, respectively. Also, in the presence of hydrogen peroxide, the % degradation in the case of using OL and OS samples is 100 % after 35 and 25 min, respectively.     

Reducibly degradable hydrogels of PNIPAM and PDMAEMA: Synthesis,stimulus‐response and drug release

Reducibly degradable hydrogels of poly(N‐isopropylacrylamide) (PNIPAM) and poly(N,N‐dimethylaminoethyl methacrylate) (PDMAEMA) were synthesized by the combination of reversible addition‐fragmentation chain transfer (RAFT) polymerization and click chemistry. The alkyne‐pending copolymer of PNIPAM or PDMAEMA was obtained through RAFT copolymerization of propargyl acrylate with NIPAM or DMAEMA. Bis‐2‐azidyl‐isobutyrylamide of cystamine (AIBCy) was used as the crosslinking reagent to prepare reducibly degradable hydrogels by click chemistry. The hydrogels exhibited temperature or pH stimulus‐responsive behavior in water, with rapid response, high swelling ratio, and reproducible swelling/shrinkage cycles. The loading and release of ceftriaxone sodium proved the feasibility of the hydrogels as the stimulus‐responsive drug delivery system. Furthermore, the presence of disulfide linkage in AIBCy favored the degradation of hydrogels in the reductive environment. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3604–3612, 2010     

双(烷氧-亚胺芳氧)基钛(IV)配合物催化D,L-丙交酯开环聚合、动力学及机理

合成了双(烷氧-亚胺芳氧)基钛(IV)配合物, 通过IR, ¹H NMR和元素分析对其进行表征, X射线单晶衍射测定了其晶体结构. 单晶结构分析表明, 该晶体属于三斜晶系, 空间群为P , a＝14.294(9) Å, b＝16.206(10) Å, c＝18.458(12) Å, V＝3911(4) ų, D_c＝1.098 g•cm^－3, μ＝0.262 mm^－1, F(000)＝1589, Z＝2, R₁＝0.081, wR₂＝0.240. 实验结果表明该配合物在130 ℃以上能引发D,L-丙交酯单体开环聚合, 可得数均分子量(M_n)为8.8×10⁴ g/mol的聚(D,L-乳酸)(PDLLA). 动力学研究表明该聚合反应对D,L-丙交酯单体浓度和催化剂浓度分别呈2级和1级, 表观活化能和频率因子分别为76.63 kJ/mol和2.91×10¹¹. 通过苄基封端聚合物¹H NMR谱的研究, 表明钛配合物引发D,L-丙交酯开环聚合是基于以Ti-O键为活性中心引发D,L-丙交酯单体酰氧键断裂开环聚合的“配位-插入”机理.     

Symmetrical polymer systems prepared using a degradable bifunctional atom transfer radical polymerization initiator: Synthesis,characterization, and cleavage

Linear (co)polymers and dimethacrylate‐end‐linked polymer networks of methyl methacrylate with 2‐(dimethylamino)ethyl methacrylate, cleavable in the middle of the polymer chain, either under thermolysis or alkaline hydrolysis conditions, were prepared via atom transfer radical polymerization (ATRP) using a specially designed bifunctional degradable initiator. This initiator was 2,6‐pyridinediethanol di(2‐bromo‐2‐methyl propanoate) (PyDEDBrMeP), bearing two 2‐(pyridin‐2‐yl)ethyl ester moieties, known for their thermal and hydrolytic (alkaline conditions) lability. As a control, a more stable bifunctional ATRP initiator, 2,6‐pyridinedimethanol di(2‐bromo‐2‐methyl propanoate) (PyDMDBrMeP), was also synthesized together with the corresponding linear polymers and polymer networks prepared from it. Thermal or hydrolytic treatment of the polymers prepared using PyDEDBrMeP led to a reduction in the molecular weights of the linear polymers by a factor of two, and to the conversion of the polymer networks to soluble branched (star) structures, consistent with the expected cleavage of the initiator residue located in the middle of the polymer chain. Thermal treatment of the polymers prepared using PyDMDBrMeP did not affect their molecular weight due to the thermal stability of the (pyridin‐2‐yl)methyl ester group, while treatment under alkaline hydrolysis conditions resulted in complete cleavage, similar to the PyDEDBrMeP‐prepared polymers. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 2342–2355