Novel synthesis of biodegradable poly(lactide-co-ethylene glycol) block copolymers

Biodegradable and amphiphilic diblock copolymers [polylactide-block-poly(ethylene glycol)] and triblock copolymers [polylactide-block-poly(ethylene glycol)-block-polylactide] were synthesized by the anionic ring-opening polymerization of lactides in the presence of poly(ethylene glycol) methyl ether or poly(ethylene glycol) and potassium hexamethyldisilazide as a catalyst. The polymerization in toluene at room temperature was very fast, yielding copolymers of controlled molecular weights and tailored molecular architectures. The chemical structure of the copolymers was investigated with ¹H and ¹³C NMR. The formation of block copolymers was confirmed by ¹³C NMR and differential scanning calorimetry investigations. The monomodal profile of the molecular weight distribution by gel permeation chromatography provided further evidence of block copolymer formation as well as the absence of cyclic species. Additional confirmation of the block copolymers was obtained by the substitution of 2-butanol for poly(ethylene glycol); butyl groups were clearly identified by ¹H NMR as polymer chain end groups. The effects of the copolymer composition and lactide stereochemistry on the copolymer properties were examined. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 2235–2245, 2007     

Poly[N‐isopropyl acrylamide]‐co‐polyurethane copolymers for controlled release of urea

A novel block copolymer of poly[N‐isopropyl acrylamide]‐co‐polyurethane was designed, synthesized, and applied as controlled release fertilizer coating. Structural confirmation of the copolymer was performed using FTIR and ¹H‐NMR spectra and elemental analysis. The coating process consists essentially of immersing urea granules in molten polymer and removing the coated urea from the melt by centrifugal action. The morphology of the coated urea was studied using scanning electron microscope (SEM). The polymer coat of the urea granules was found to swell in water forming pores and enabling the release of urea. The urea released from the granule, monitored using a mass spectroscopy technique, was found to be governed by pH of the aqueous medium. The study anticipates development of a beneficiary fertilizer coat in terms of improving controlled release over a period of time which can be tailored by soil temperature, pH and moisture. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3236–3243, 2010     

Novel synthesis of biodegradable linear and star block copolymers based on ε‐caprolactone and lactides using potassium‐based catalyst

Biodegradable, triblock poly(lactide)‐block‐poly(ε‐caprolactone)‐block‐poly(lactide) (PLA‐b‐PCL‐b‐PLA) copolymers and 3‐star‐(PCL‐b‐PLA) block copolymers were synthesized by ring opening polymerization of lactides in the presence of poly(ε‐caprolactone) diol or 3‐star‐poly(ε‐caprolactone) triol as macroinitiator and potassium hexamethyldisilazide as a catalyst. Polymerizations were carried out in toluene at room temperature to yield monomodal polymers of controlled molecular weight. The chemical structure of the copolymers was investigated by ¹H and ¹³C‐NMR. The formation of block copolymers was confirmed by NMR and DSC investigations. The effects of copolymer composition and molecular structure on the physical properties were investigated by GPC and DSC. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5363–5370, 2008     

生物降解性聚酯

本文阐述了生物降解性聚酯的主要产品，生物降解性聚酯的降解机理及生物降解性聚合物的存在问题和研究方向．     

生物降解型聚氨酯研究进展

本文综述了生物降解型聚氨酯的研究现状，并探讨了影响其生物降解性的因素，指出了其应用前景，特别是医学上的应用．     

Synthesis and aggregation behavior of chitooligosaccharide‐based biodegradable graft copolymers

A series of novel “jellyfish‐like” graft copolymers with chitooligosaccharide (COS) as shorter backbone and poly(ε‐caprolactone) as longer branches were synthesized using ring‐opening polymerization of ε‐caprolactone via a protection‐polymerization‐deprotection procedure with trimethylsilylchitooligosaccharide as intermediate and triethylaluminum as catalyst precursor. The obtained chitooligosaccharide‐graft‐poly(ε‐caprolactone) polymers possess amphiphilic structure with hydrophilic COS backbone and hydrophobic polycaprolactone branches. Because of this unique “jellyfish‐like” structure, these graft copolymers could self‐assemble to form various morphologies of aggregates in a mixture solution of water and tetrahydrofuran. The transmission electron microscopy studies revealed that the formed aggregates exhibited necklace‐like, flower‐like onion vesicle, and tubular morphologies. It is found that the hydrogen‐bonding formed by the hydroxyl and amino groups remained on the COS backbone played an important role during the aggregation of these graft copolymers, and their morphologies were changed with the varying length of poly (ε‐caprolactone) branches, the concentration of the graft copolymer, and the self‐assembly process. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4889–4904, 2008     

Fully biodegradable polymeric micelles based on hydrophobic‐ and hydrophilic‐functionalized poly(lactide) block copolymers

Novel amphiphilic diblock copolymers from a combination of hydrophobic‐functional poly(lactides) (PLAs) with hydrophilic‐functional PLAs or poly(malic acid), respectively, toward fully biodegradable materials for medical applications, such as micellar drug delivery systems, are reported for the first time. The presented PLA‐based polymeric micelles are characterized by their small size below 100 nm, low critical micellar concentrations, good in vitro stabilities at room and body temperature, and efficient incorporation capability of hydrophobic compounds, particularly with regard to potential drug substances. Moreover, the advantage of being totally degradable with different rates at different pH values, as investigated in medical cancer treatment, is demonstrated. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3244–3254, 2010     

Dendritic surface functionalization of biodegradable polymer assemblies

The functionalization of nanomaterials with dendritic surface moieties was recently demonstrated to be an effective means of displaying biological ligands and potentially modulating the biological properties of these materials. With the aim of extending this surface functionalization approach to biodegradable polymer assemblies, poly(ethylene oxide)‐polycaprolactone (PEO‐PCL) block copolymers with terminal azide or methoxy groups were prepared and were assembled to form micelles or vesicles with varying loadings of surface azides. Dendrons bearing peripheral amines, guanidines, or hydroxyls were prepared and conjugated to the assemblies, and the conjugation yields were measured and compared as a function of azide loading and assembly type (micelle versus vesicle). A small molecule rhodamine derivative was also conjugated, allowing the effect of sterics to be studied. The effects of the surface functionalization on the aggregation state of the assemblies were studied by light scattering and transmission electron microscopy. Overall, the results revealed interesting differences between the two systems with respect to both the reaction yields and the stabilities. Furthermore, micelles functionalized with dendrons bearing peripheral guanidines were found to exhibit enhanced cell uptake relative to control micelles, demonstrating that this approach can be used to modulate the biological properties of the materials. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Nanofibers by Green Electrospinning of Aqueous Suspensions of Biodegradable Block Copolyesters for Applications in Medicine,Pharmacy and Agriculture

Poly(hexamethylene adipate)‐PEO block copolymers (PHA‐b‐PEO) with different PEO contents were synthesized and processed to aqueous suspensions with high solid contents by a solvent displacement method followed by dialysis. The best suspension displayed a solid content of 16 wt.‐% and an average particle size of 108 nm. This suspension was mixed with a small amount of high molecular weight PEO and Brij78 and electrospun into corresponding nanofibers. After extraction with water, nanofibers of PHA‐b‐PEO were obtained. Electrospinning of aqueous suspensions of biodegradable polyesters alleviates concerns regarding safety, toxicology and environmental problems, which are associated with spinning of such polyesters from harmful organic solvents and thereby offers novel perspectives for applications in medicine, pharmacy and agriculture. Electrospinning of polymers from aqueous suspensions avoiding harmful organic solvents is suggested to be “green electrospinning”.

     

Biomedical applications of biodegradable polymers

Utilization of polymers as biomaterials has greatly impacted the advancement of modern medicine. Specifically, polymeric biomaterials that are biodegradable provide the significant advantage of being able to be broken down and removed after they have served their function. Applications are wide ranging with degradable polymers being used clinically as surgical sutures and implants. To fit functional demand, materials with desired physical, chemical, biological, biomechanical, and degradation properties must be selected. Fortunately, a wide range of natural and synthetic degradable polymers has been investigated for biomedical applications with novel materials constantly being developed to meet new challenges. This review summarizes the most recent advances in the field over the past 4 years, specifically highlighting new and interesting discoveries in tissue engineering and drug delivery applications. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011     

Linear polyurethanes made from threitol: Acetalized and hydroxylated polymers

A set of novel linear polyurethanes was synthesized by reaction in solution of 1,6‐hexamethylene diisocyanate (HDI) or 4,4′‐methylene‐bis(phenyl diisocyanate) with 2,3‐acetalized threitols, specifically, 2,3‐O‐methylidene‐L ‐threitol and 2,3‐O‐isopropylidene‐D ‐threitol. The polyurethanes containing acetalized threitols had weight‐average molecular weights between 40,000 and 65,000 Da. Most of them were amorphous and they displayed T_g higher than their unsubstituted analogs. Deprotection of acetalized polyurethanes by treatment with acid allowed preparing semicrystalline polyurethanes bearing two free hydroxyl groups in the repeating unit. The crystalline structure and crystallizability of the hydroxylated polyurethane made from HDI were investigated taken as reference the polyurethane made from 1,4‐butanediol and HDI. The hydrolytic degradability of threitol derived polyurethanes was comparatively evaluated under a variety of conditions. Highest degradation rates were obtained upon incubation at pH 10 at temperatures above T_g, the aliphatic hydroxylated polyurethane being the fastest degrading compound. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7996–8012, 2008     

Novel photopolymerizable biodegradable triblock polymers for tissue engineering scaffolds: synthesis and characterization

For use in micro-patterned scaffolds in tissue engineering, novel diacrylated triblock macromers (PLA-b-PCL-b-PLA, PGA-b-PCL-b-PGA and PCL-b-PEO-b-PCL) were synthesized and characterized by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR) and gel permeation chromatography (GPC). All diacrylated polymers were designed as triblock copolymers and involved biodegradable blocks of relatively non-polar epsilon-caprolactone (CL) and polar monomers such as glycolide (GA), lactide (LA) or ethylene oxide (EO). All triblock polymers were prepared in molecular weights of a few kilo daltons via the anionic ring-opening polymerization (ROP) of the corresponding lactide, glycolide or caprolactone using stannous octoate [Sn(Oct)(2)] as catalyst. The polymers had low polydispersity indices, ranging from 1.23 to 1.56. Biodegradable polymeric networks were prepared with conversions of 72-84% via photopolymerization of the triblock diacrylated polymers with 2,2-dimethoxy-2-phenylacetophenone (DMPA) as photoinitiator. PLA-b-PCL-b-PLA copolymers crumbled easily and were not suitable for micro-patterning. PGA-b-PCL-b-PGA copolymers had higher water contact angles than PCL-b-PEO-b-PCL and were also cytocompatible with Fibroblasts 3T3.     

Synthesis and characterization of biodegradable A–B–A triblock copolymers containing poly(ϵ‐caprolactone) A blocks and poly(trans‐4‐hydroxy‐L‐proline) B blocks

Novel, biodegradable poly(?‐caprolactone)‐block‐poly(trans‐4‐hydroxy‐N‐benzyloxycarbonyl‐L ‐proline)‐block‐poly(?‐caprolactone) triblock copolymers were synthesized by ring‐opening polymerization from dihydroxyl‐terminated macroinitiator poly(trans‐4‐hydroxy‐N‐benzyloxycarbonyl‐L ‐proline) (PHpr) and ?‐caprolactone (?‐CL) with stannous octoate as the catalyst. The molecular weights were characterized with gel permeation chromatography and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry. With an increase in the contents of ?‐CL incorporated into the copolymers, a decrease in the glass‐transition temperature (T_g) was observed. The T_g values of copoly(4‐phenyl‐?‐caprolactone) and copoly(4‐methyl‐?‐caprolactone) were higher than T_g of copoly(?‐caprolactone). Their micellar characteristics in an aqueous phase were investigated with fluorescence spectroscopy, dynamic light scattering, and transmission electron microscopy. The block copolymers formed micelles in the aqueous phase with critical micelle concentrations in the range of 1.00–1.36 mg L^?1. With higher molecular weights and hydrophobic components in the copolymers, a higher critical micelle concentration was observed. As the feed weight ratio of antitriptyline hydrochloride (AM) to the polymer increased, the drug loading increased. The micelles exhibited a spherical shape, and the average size was less than 250 nm. The in vitro hydrolytic degradation and controlled drug release properties of the triblock copolymers were also investigated. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 4268–4280, 2006     

A novel and versatile potassium‐based catalyst for the ring opening polymerization of cyclic esters

Poly(lactide) (PLA), poly(ε‐caprolactone) (PCL) and poly(trimethylene carbonate) (PTMC) homopolymers of high molecular weight were prepared using potassium‐based catalyst. Polymerizations were carried out in toluene at room temperature. The chemical structure of the polymers was investigated by ¹H and ¹³C NMR. The physical properties investigated by GPC and DSC for the polymers obtained are similar to those prepared using tin octanoate based catalyst. Using a sequential polymerization procedure, PLA‐b‐PCL, PLA‐b‐PTMC, and PCL‐b‐PTMC diblock copolymers were synthesized and characterized in terms of their composition and physical properties. The formation of diblock copolymers was confirmed by NMR and DSC measurements. In vitro cytotoxicity tests have been carried out using MTS assay and the results show the biocompatibility of these polymers in the presence of the fibroblast cells. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5348–5362, 2008     

Novel biodegradable copolyesters containing blocks of poly(3-hydroxyoctanoate) and poly(epsilon-caprolactone): synthesis and characterization

Novel biodegradable polyester block copolymers have been synthesized by using well-defined poly(3-hydroxyoctanoate) (PHO) oligomers having a hydroxyl end group and an ester end group with M(n) values of 800, 2,500, 5,300, 8,000, or 20,000 as an elastomeric soft segment and poly(epsilon-caprolactone) as a more crystalline segment. These PHO oligomers prepared by methanolysis were subjected to block copolymerization with epsilon-caprolactone. The chemical structure of the copolymers was confirmed by (1)H NMR and (13)C NMR spectroscopy. All the copolyesters are semi-crystalline and two T(g) were observed by differential scanning calorimetry when the molecular weight of the PHO block is about 20,000.     

Synthesis of electroactive and biodegradable multiblock copolymers based on poly(ester amide) and aniline pentamer

A new family of multiblock copolymers (PEA‐b‐AP) based on poly(ester amide) (PEA) and aniline pentamer (AP) with the unique properties of being both electroactive and biodegradable was synthesized via a two‐stage active solution polycondensation. The new synthesis approach proceeded smoothly, and avoided the complicated purification steps for separating the intermediate products. The molecular weight of PEA blocks was regulated by varying the nucleophilic/electrophilic monomers feed ratios. The chemical structures of the copolymers were confirmed by both IR and NMR spectra. UV‐Vis spectroscopy indicated that the copolymers possessed of the intrinsic electroactivity of AP blocks, and showed three reversible oxidation states. The copolymers had lower degradation rates than the PEA homopolymers with similar molecular weight, and their degradation rates were greatly affected by the proportion of AP blocks. In vitro cell culture studies of the PEA‐b‐APs revealed that they facilitated the proliferation of RSC96 Schwann cells and displayed a good biocompatibility. These biodegradable copolymers with electroactive function may have great potential for use as nerve repair and regeneration scaffold materials in tissue engineering. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 4722–4731     

A novel approach to biodegradable block copolymers of epsilon-caprolactone and delta-valerolactone catalyzed by new aluminum metal complexes

The chemical preparation of structurally well-defined biodegradable amphiphilic block copolymers is now of great interest for biomedical applications and the fundamental mimetic study of biomacromolecule self-assembly. For this purpose, in this study, (R,R)-N,N'-bis(3-tert-butylsalicylidene)-1,2-cyclohexanediamine 2 as a ligand was first synthesized from 1,2-cyclohexanediamine (DACH) and was allowed to further react with AlMe3, leading to a precursor compound 3. Then, the novel five-coordinated aluminum metal complexes 4-6 and 7-8 were prepared with good yields of 80-90%, bearing various molar mass monofunctional methoxy-poly(ethylene glycol) MPEG and difunctional poly(ethylene glycol) PEG as the alkoxy moieties, respectively. By means of nuclear magnetic resonance spectrometry (NMR), mass spectrometry (MALDI-FTMS) and Fourier Transform infrared spectrometry (FT-IR), new metal aluminum complexes 4-8 were characterized as having distinct chemical structures. Utilizing the synthesized metal complexes 4-8 as novel coordination polymerization catalytic templates, biodegradable amphiphilic MPEG-b-PCL, MPEG-b-PVL, PCL-b-PEG-b-PCL and PVL-b-PEG-b-PVL were synthesized with good control of the molecular weight distribution via the ring opening polymerization of epsilon-caprolactone and delta-valerolactone monomers at 100 degrees C in toluene. In addition, the chemical and crystalline structures and the thermal properties of these block biodegradable copolymers were analyzed by means of NMR, gel permeation chromatography (GPC), wide-angle X-ray diffraction (WAXD), differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA). It was found that the melting points and crystallinities of the block copolymers synthesized strongly depended on the molecular structures of the polyether and polyester building blocks. Only one glass transition stage was detected, indicating good chain/segmental miscibility between the hydrophilic MPEG/PEG and hydrophobic PCL/PVL blocks in the non-crystalline regions. Moreover, TGA analysis exhibited typical two-step decomposition profiles with the weight-loss percentages in good agreement with block compositions from NMR calculations.     

Thermosensitive biodegradable polydepsipeptide

A poly(N-isopropylacrylamide) (PNIPAAm)-like biodegradable thermosensitive polydepsipeptide, poly[Glc-Asn(N-isopropyl)], was synthesized by introducing an isopropyl amide group into poly[Glc-Asn]. Poly[Glc-Asn(N-isopropyl)] was degraded in vitro by cleavage of the ester bonds in the main chain in water at room temperature. The non-toxic nature of the polymer and its degradation products, coupled with a cloud point at 29 degrees C in water, make this polymer attractive for biomedical implant applications.     

Synthesis of amphiphilic biodegradable glycocopolymers based on poly(ε‐caprolactone) by ring‐opening polymerization and click chemistry

Amphiphilic, biodegradable block glycopolymers based on poly(ε‐caprolactone) (PCL) with various pendent saccharides were synthesized by combination of ring‐opening polymerization (ROP) and “click” chemistry. PCL macroinitiators obtained by ROP of ε‐caprolactone were used to initiate the ROP of 2‐bromo‐ε‐caprolactone (BrCL) to get diblock copolymers, PCL‐b‐PBrCL. Reaction of the block copolymers with sodium azide converted the bromine groups in the PBrCL block to azide groups. In the final step, click chemistry of alkynyl saccharides with the pendent azide groups of PCL‐b‐PBrCL led to the formation of the amphiphilic block glycopolymers. These copolymers were characterized by ¹H NMR spectroscopy and gel permeation chromatography. The self‐assembly behavior of the amphiphilic block copolymers was investigated using transmission electron microscopy and atomic force microscope, spherical aggregates with saccharide groups on the surface were observed, and the aggregates could bind reversibly with Concanavalin A. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3583–3594, 2009     

Fusiform micelles from nonlinear poly(ethylene glycol)/polylactide copolymers as biodegradable drug carriers

PEG-PLA copolymers with dumbbell- and Y-shaped structures are prepared. They can self-assemble from nanoparticles to micro-sized fusiform micellar particles in aqueous solution. In particular the micelles formed by the (PLA)2-PEG-(PLA)2 particles show a better drug loading capacity and encapsulation efficiency than those formed by linear MPEG-PLA. In vitro studies show that the particles formed by Y-shaped copolymers show a particularly quick drug release. The copolymers have good biocompatibility with low cytotoxicity. These unique self-assembled systems thus have many possible biomedical applications, such as a sustained delivery of high-dosed water insoluble drugs, quick effective drugs for trauma, controlled delivery of the oral-administration drugs, and so forth.