Preparation and characterization of biodegradable nanoparticles based on amphiphilic poly(3-hydroxybutyrate)-poly(ethylene glycol)-poly(3-hydroxybutyrate) triblock copolymer

Amphiphilic triblock copolymers of poly(3-hydroxybutyrate)-poly(ethylene glycol)-poly(3-hydroxybutyrate) (PHB-PEG-PHB) were directly synthesized by the ring-opening copolymerization of β-butyrolactone monomer using PEG as macroinitiator. Their structure, thermal properties and crystallization were investigated by ¹H NMR, differential scanning calorimetry (DSC) and X-ray diffraction. It was found that both PHB and PEG blocks were miscible. With the increase in the PHB block length, the triblock copolymers became amorphous because amorphous PHB block remarkably depressed the crystallization of the PEG block. Biodegradable nanoparticles with core-shell structure were prepared in aqueous solution from the amphiphilic triblock copolymers, and characterized by ¹H NMR, SEM and fluorescence. The hydrophobic PHB segments formed the central solid-like core, and stabilized by the hydrophilic PEG block. The nanoparticle size was close related to the initial concentrations of the nanoparticle dispersions and the compositions of the triblock copolymers. Moreover, the PHB-PEG-PHB nanoparticles also showed good drug loading properties, which suggested that they were very suitable as delivery vehicles for hydrophobic drugs.     

Novel synthesis of biodegradable amphiphilic linear and star block copolymers based on poly(ε‐caprolactone) and poly(ethylene glycol)

Biodegradable, amphiphilic, diblock poly(ε‐caprolactone)‐block‐poly(ethylene glycol) (PCL‐b‐PEG), triblock poly(ε‐caprolactone)‐block‐poly(ethylene glycol)‐block‐poly(ε‐caprolactone) (PCL‐b‐PEG‐b‐PCL), and star shaped copolymers were synthesized by ring opening polymerization of ε‐caprolactone in the presence of poly(ethylene glycol) methyl ether or poly(ethylene glycol) or star poly(ethylene glycol) 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 ¹³C NMR and DSC investigations. The effects of copolymer composition and molecular structure on the physical properties were investigated by GPC and DSC. For the same PCL chain length, the materials obtained in the case of linear copolymers are viscous whereas in the case of star copolymer solid materials are obtained with low T_g and T_m temperatures. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3975–3985, 2007     

Synthesis of end‐functionalized AB copolymers. II. Synthesis and characterization of carboxyl‐terminated poly(ethylene glycol)–poly(amino acid) block copolymers

AB block copolymers composed of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic poly(amino acid) with a carboxyl group at the end of PEG were synthesized with α‐carboxylic sodium‐ω‐amino‐PEG as a macroinitiator for the ring‐opening polymerization of N‐carboxy anhydride. Characterizations by ¹H NMR, IR, and gel permeation chromatography were carried out to confirm that the diblock copolymers were formed. In aqueous media this copolymer formed self‐associated polymer micelles that have a carboxyl group on the surface. The carboxyl groups located at the outer shell of the polymeric micelle were expected to combine with ligands to target specific cell populations. The diameter of the polymer micelles was in the range of 30–80 nm. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3527–3536, 2004     

Thermogelling polymers composed of poly(cyclohexylenedimethylene adipate) and poly(ethylene glycol)

Block copolymers composed of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic biodegradable polyesters have been reported as thermogelling polymers, because they feature temperature-dependent sol-to-gel or gel-to-sol transitions in aqueous solutions. In this study, a series of thermogelling poly(ethylene glycol methyl ether)-block–poly(cyclohexylenedimethylene adipate)-block–poly(ethylene glycol methyl ether) triblock copolymers and PEG-block–poly(cyclohexylenedimethylene adipate) multiblock copolymers was synthesized by reacting hydroxyl-terminated poly(cyclohexylenedimethylene adipate) (PCA) with poly(ethylene glycol methyl ether) and PEG, respectively, using 1,6-diisocyanatohexane as the coupling agent. Two hydroxyl-terminated PCAs, i.e., poly(1,4-cyclohexylenedimethylene adipate) and poly(1,3/1,4-cyclohexylenedimethylene adipate), were synthesized by the condensation reaction of adipic acid (AA) with 1,4-cyclohexanedimethanol (CHDM) and 1,3/1,4-CHDM, respectively, and used as the hydrophobic polyester blocks of these thermogelling copolymers to compare the effect of crystallinity on the sol-to-gel transition behavior.The polymers were characterized using proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, gel permeation chromatography, differential scanning calorimetry, solubility testing, and rheological analysis. Experimental results revealed that the structure of the PCA block (crystalline vs. amorphous), the molecular weights of the hydrophobic PCA and hydrophilic PEG blocks, and the type of thermogelling polymer (triblock vs. multiblock) influenced the solubility, polymer micelle packing characteristics, maximum storage modulus, and sol-to-gel temperature of the polymers. Among all the samples at 40 wt.% aqueous solutions, triblock copolymer TB3 showed sol-to-gel temperature at 22 °C, and had the highest maximum storage modulus about 170 Pa.     

Application of New Modified Poly(ethylene Oxide)-Block-Poly(propylene oxide)-Block-Poly(ethylene oxide) Copolymers as Demulsifier for Petroleum Crude Oil Emulsion

Water soluble nonionic amphiphilic block copolymers based on hydrophilic poly(ethylene glycol) (PEG) and hydrophobic poly(propylene glycol) (PPG) were prepared. Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) copolymers, PEG-PPG-PEG, were prepared in the normal condition. The chemical composition and molecular weights of the prepared copolymers were determined from ¹H NMR and GPC techniques. The surface properties of the prepared surfactants were determined by measuring the surface tension at different temperatures. The prepared nonionic surfactants were evaluated as demulsifiers for water in crude-oil emulsions that were pronounced at different ratios of crude oil: water at 318 K and 333 K. The experimental results showed that the dehydration rate of the prepared demulsifiers reached 100% based on demulsifier chemical compositions and concentrations.     

Probing the micellization of diblock and triblock copolymers of poly(<Emphasis Type="SmallCaps">l</Emphasis>-lactide) and poly(ethylene glycol) in aqueous and NaCl salt solutions

The micelle formation of a series of amphiphilic block copolymers in aqueous and NaCl solutions was studied by a fluorescent probe technique using pyrene as a "model drug". These copolymers were synthesized from poly (ethylene glycol) (PEG) and l-lactide by a new calcium ammoniate catalyst. They had fixed PEG block lengths (44, 104 or 113 ethylene oxide units) and various poly(l-lactide) (PLLA) block lengths (15–280 lactide units). The critical micelle concentration (cmc) was found to decrease with increasing PLLA content. The distinct dissimilarity of the cmc values of diblock and triblock copolymers based on the same block length of PEG provided evidence for the different configurations of their micelles. It was also observed that the introduction of NaCl salt significantly contributed to a decrease in the cmcs of the copolymers with short PEG and PLLA blocks, while it had less influence on the cmcs of copolymers with long PEG or PLLA blocks. The dependence of partition coefficients ranging from 0.2×10⁵ to 1.9×10⁵ on the PLLA content in the copolymer and on the micelle configuration was also discussed. The contribution of NaCl salt to increasing the partition of pyrene into a micellar phase was observed.     

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     

Synthesis and micellization of amphiphilic poly(sebacic anhydride)–poly(ethylene glycol)–poly(sebacic anhydride) block copolymers

Amphiphilic biodegradable block copolymers [poly(sebacic anhydride)–poly(ethylene glycol)–poly(sebacic anhydride)] were synthesized by the melt polycondensation of poly(ethylene glycol) and sebacic anhydride prepolymers. The chemical structure, crystalline nature, and phase behavior of the resulting copolymers were characterized with ¹H NMR, Fourier transform infrared, gel permeation chromatography, and differential scanning calorimetry. Microphase separation of the copolymers occurred, and the crystallinity of the poly(sebacic anhydride) (PSA) blocks diminished when the sebacic anhydride unit content in the copolymer was only 21.6%. ¹H NMR spectra carried out in CDCl₃ and D₂O were used to demonstrate the existence of hydrophobic PSA domains as the core of the micelle. In aqueous media, the copolymers formed micelles after precipitation from water‐miscible solvents. The effects on the micelle sizes due to the micelle preparation conditions, such as the organic phase, dropping rate of the polymer organic solution into the aqueous phase, and copolymer concentrations in the organic phase, were studied. There was an increase in the micelle size as the molecular weight of the PSA block was increased. The diameters of the copolymer micelles were also found to increase as the concentration of the copolymer dissolved in the organic phase was increased, and the dependence of the micelle diameters on the concentration of the copolymer varied with the copolymer composition. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 1271–1278, 2006     

Triblock copolymers of lactide with poly(ethylene glycol) and influence of stereochemical composition

Polymerization of L-lactide (LLA) and poly(ethylene glycol) (PEG) at 120°C using stannous 2-ethyl hexanoate results in ABA triblock copolymers in good yields. The glass transition temperature of the copolymers shows strong dependence on the composition. One- and two-phase triblock copolymers can be prepared by controlling the molecular weight of the PEG soft block, as well as the initial LLA/PEG charge ratio. Incorporation of racemic lactide during polymerization drastically affects the crystallinity of the block copolymers obtained. ¹H and ¹³C (solid state) NMR are powerful tools for characterization of the polymer materials.     

Effect of block lengths on the association behavior of poly(l-lactic acid)/poly(ethylene glycol) (PLA–PEG–PLA) micelles in aqueous solution

A series of poly(l-lactic acid)/poly(ethylene glycol) triblock copolymers with a PLA–PEG–PLA architecture were synthesized by a ring-opening polymerization (ROP) process. The copolymers were characterized by ¹H NMR and GPC. The total number average molecular weights were in the range of 4,700–50,000, whereas the degrees of polymerization of the PLA and PEG blocks varied from 15 to 359 and from 68 to 136, respectively. The self-association of these copolymers in aqueous environment was studied by emission fluorescence spectroscopy of anilinonaphthalene probe and the critical association concentration (CAC) of the copolymers was measured. It was found that the micellization process of these copolymers was mainly determined by the length of the hydrophobic LA block, while the length of the hydrophilic PEG block had little effect. Furthermore, the low CAC values of the copolymers suggest that the copolymers form stable supramolecular structures in aqueous solutions.     

New architectures of poly(ethylene glycol) and poly(methylthiirane) in block copolymers

Two synthetic ways were experimented to prepare new architectures of block copolymers made of poly(ethylene glycol) (PEG) and poly(methylthiirane). The coupling of both blocks conveniently end-capped as well as anionic polymerization of methylthiirane initiated by PEG-thiols gave readily the copolymers. Their characterization by ¹H NMR, SEC and IR confirmed the expected structures.     

Synthesis of novel biodegradable poly(ethylene glycol) analogue:Water-soluble aliphatic polyester with pendant oligo(ethylene glycol) chains

A novel poly(ethylene glycol)(PEG) analogue composed of aliphatic polyester backbone and pendant oligo(ethylene glycol) short chains is reported.The PEG analogue is a copolymer synthesized by ring-opening alternating copolymerization of succinic anhydride with 2-((2-(2-metho xyethoxy)ethoxy)methyl)oxirane.The structure of the copolymer was confirmed by ~1H NMR spectrum.The effects of the monomer feed ratio on the copolymerization were studied and the polymerization mechanism was given.The PEG analogue di...     

Amphiphilic Biodegradable Poly(ϵ-caprolactone)-Poly(ethylene glycol) – Poly(ϵ-caprolactone) Triblock Copolymer Synthesis by Maghnite-H+ as a Green Catalyst

Amphiphilic biodegradable (PCL-PEG-PCL) triblock copolymers have been successfully prepared by the ring opening polymerization of ?-caprolactone (CL) in the presence of poly(ethylene glycol) (PEG) at 80°C employing Maghnite-H⁺ a non-toxic Montmorillonite clay as catalyst. Maghnite-H⁺ reacts as a solid source of protons to induce ?-caprolactone polymerization. The triblock architecture, molecular weight and thermal properties of the copolymers were characterized by NMR spectra, GPC and DSC analyses. The effect of Maghnite-H⁺ proportion and PEGs on the rate of copolymerization and on average molecular weight of resulting copolymers was studied. A cationic mechanism for the copolymerization reaction was proposed.     

ABA-type amphiphilic triblock copolymers containing p-ethoxy azobenzene via atom transfer radical polymerization: Synthesis,characterization, and properties

ABA-type amphiphilic triblock copolymers composed of poly(ethylene glycol)s (PEGs) with different number-average molecular weights as the hydrophilic blocks (B) and poly{6-[4-(4-ethoxyphenylazo)phenoxy]hexyl methacrylate} (PA6C) as the hydrophobic blocks (A) were prepared via atom transfer radical polymerization. These copolymers were prepared from bromo-terminated macroinitiators based on PEG6000, PEG2000, and PEG600, with CuBr/N,N,N′,N″,N″-pentamethyldiethylenetriamine as the catalytic system, at 85 °C in anisole. The block copolymers were characterized with ¹H NMR spectroscopy and gel permeation chromatography. Differential scanning calorimetry measurements were performed to reveal the phase segregation. In contrast to those polymers with similar compositions and structures in previous reports, these amphiphilic copolymers exhibited unusual liquid-crystalline properties over a wide temperature range, being stable even at room temperature. These copolymers showed photoresponsive isomerization under the irradiation of UV–vis light both in THF solutions and in solid films. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 2225–2234, 2007     

Synthesis and characterization of well‐defined diblock and triblock copolymers of poly(N‐isopropylacrylamide) and poly(ethylene oxide)

Well‐defined diblock and triblock copolymers composed of poly(N‐isopropylacrylamide) (PNIPAM) and poly(ethylene oxide) (PEO) were successfully synthesized through the reversible addition–fragmentation chain transfer polymerization of N‐isopropylacrylamide (NIPAM) with PEO capped with one or two dithiobenzoyl groups as a macrotransfer agent. ¹H NMR, Fourier transform infrared, and gel permeation chromatography instruments were used to characterize the block copolymers obtained. The results showed that the diblock and triblock copolymers had well‐defined structures and narrow molecular weight distributions (weight‐average molecular weight/number‐average molecular weight < 1.2), and the molecular weight of the PNIPAM block in the diblock and triblock copolymers could be controlled by the initial molar ratio of NIPAM to dithiobenzoate‐terminated PEO and the NIPAM conversion. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4873–4881, 2004     

Amphiphilic Seven-arm Star Triblock Copolymers with Diverse Morphologies in Aqueous Solution Induced by Crystallization and pH

Well-defined amphiphilic seven-arm star triblock copolymers containing hydrophobic crystalline poly(ε-caprolactone)(PCL) blocks, hydrophobic non-crystalline poly(tert-butyl acrylate)(PtBA) blocks and hydrophilic poly(ethylene glycol)(PEG) blocks were precisely synthesized by a combination of ring-opening polymerization(ROP), atom transfer radical polymerization(ATRP) and “click” reaction. Such star copolymers could self-assemble into “core-shell-corona” micelles and “multi-layer” vesicles depending on the fraction of each block. Meanwhile, the selective hydrolysis of middle PtBA blocks into the poly(acrylic acid)(PAA) blocks allowed the star block copolymers to further change their morphologies of aqueous aggregates in response to pH values.     

Synthesis and characterization of poly(ϵ-caprolactone)-poly(ethylene glycol) block copolymer

Poly(ϵ-caprolactone)–poly(ethylene glycol)–poly(ϵ-caprolactone) triblock copolymers (PECL) covering a wide range of poly(ethylene glycol) (PEG) lengths were synthesized with alkali metal alkoxide derivatives of poly(ethylene glycol). The effects of various factors, such as amount of the initiator, reaction time and temperature, polarity of solvent, length of PEG segment, and counterion on the polymerization were investigated. The copolymers were characterized by ¹H-NMR, IR, GPC, and DSC. It was found that THF system is superior to toluene system. The conversion of the monomer increased with increase of the initiator concentration. High molecular weight of the copolymer and high conversion of the monomer was obtained at below 30°C within 5 min. The polymerization process was studied by GPC and the coexistence of propagation and transesterification reaction was found, which leaded to relatively broad molecular weight distribution of the copolymers. © 1997 John Wiley & Sons, Inc.     

Preparation and characterization of poly(l,l-lactide)-b-poly(ethylene glycol)-b-poly(l,l-lactide) (PLLA-PEG-PLLA) microspheres having encapsulated tetracycline

Amphiphilic triblock copolymers, based on hydrophilic poly(ethylene glycol) (PEG) blocks and hydrophobic poly(l,l-lactide) (PLLA) blocks, were used as the matrix material for the preparation of tetracycline-loaded microspheres. The morphology and thermal properties of the biodegradable microspheres were evaluated. SEM showed the predominance of the spherical shape, however, it was possible to distinguish three patterns: rough or smooth surface or uneven collapsed volume. The FTIR analysis indicated good mechanical stability and structural integrity of the PLLA-PEG-PLLA copolymer??s microspheres enclosing tetracycline. By thermal analysis it was possible to see the marginal influence of tetracycline on the glass transition and melting temperatures of the PLLA-PEG-PLLA triblock copolymer, while the results by TG indicated the presence of tetracycline in the inner structure of the microspheres, which thermal decomposition leading to char formation was triggered by the drug??s presence.     

两亲型聚L-亮氨酸-聚乙二醇单甲醚嵌段共聚物的合成与表征

开环聚合;生物降解共聚物;两亲型聚L-亮氨酸-聚乙二醇单甲醚嵌段共聚物的合成与表征     

Poly(2-oxazoline)-Based Polyplexes as a PEG-Free Plasmid DNA Delivery Platform

The present study expands the versatility of cationic poly(2-oxazoline) (POx) copolymers as a polyethylene glycol (PEG)-free platform for gene delivery to immune cells, such as monocytes and macrophages. Several block copolymers are developed by varying nonionic hydrophilic blocks (poly(2-methyl-2-oxazoline) (pMeOx) or poly(2-ethyl-2-oxazoline) (pEtOx), cationic blocks, and an optional hydrophobic block (poly(2-isopropyl-2-oxazoline) (iPrOx). The cationic blocks are produced by side chain modification of 2-methoxy-carboxyethyl-2-oxazoline (MestOx) block precursor with diethylenetriamine (DET) or tris(2-aminoethyl)amine (TREN). For the attachment of a targeting ligand, mannose, azide-alkyne cycloaddition click chemistry methods are employed. Of the two cationic side chains, polyplexes made with DET-containing copolymers transfect macrophages significantly better than those made with TREN-based copolymer. Likewise, nontargeted pEtOx-based diblock copolymer is more active in cell transfection than pMeOx-based copolymer. The triblock copolymer with hydrophobic block iPrOx performs poorly compared to the diblock copolymer which lacks this additional block. Surprisingly, attachment of a mannose ligand to either copolymer is inhibitory for transfection. Despite similarities in size and design, mannosylated polyplexes result in lower cell internalization compared to nonmannosylated polyplexes. Thus, PEG-free, nontargeted DET-, and pEtOx-based diblock copolymer outperforms other studied structures in the transfection of macrophages and displays transfection levels comparable to GeneJuice, a commercial nonlipid transfection reagent.