Poly(ethylene glycol) (PEG2000) polymers containing one or two amine residues are linked to α‐lipoamino acids (LAA) to produce mono‐ and homo‐disubstituted PEG–LAA conjugates as new materials for the surface coating of colloidal drug carriers. Conjugates are characterized by FT‐IR, 1H‐NMR, and MALDI–TOF mass spectrometry. Differential scanning calorimetry studies are performed to assess the interaction of PEG2000–LAAs with a biomembrane model (dipalmitoylphosphatidylcholine multilamellar liposomes). Whereas the parent PEGs affect only the superficial structure of the bilayers, the amphiphilic PEG–LAA conjugates exert a modulated perturbing effect on the thermotropic profile of liposomes. A molar concentration between 5% and 10% is individuated as the more suitable to produce stable vesicles. 相似文献
Summary: 1,3,5‐Tris(4‐fluorobenzoyl)benzene (TFBB) was polycondensed with silylated 4,4′‐dihydroxybiphenyl, bisphenol‐A or 4‐tert‐butylcatechol in N‐methylpyrrolidine with K2CO3 as a promoter. The TFBB/diphenol feed ratio was varied from 1.0:1.0 to 1:0:1.5. Partial cross‐linking was observed with the stiff 4,4′‐dihydroxybiphenyl, even at the 1.0:1.0 ratio. With bisphenol‐A, no gelation took place up to a feed ratio of 1.0:1.3, indicating a high cyclization tendency. With 4‐tert‐butylcatechol, no cross‐linking occurred up to the 1.0:1.5 ratio, proving an even higher cyclization tendency. The formation of cyclic, bicyclic and multicyclic oligo‐ and polyethers was detected by means of MALDI‐TOF mass spectrometry for all reaction products. These results demonstrate that increasing chain stiffness reduces the influence of cyclization. Cyclization proved unavoidable, however, and a high cyclization tendency prevents the formation of hyperbranched and networked structures.
Polycondensations of 4,4′‐difluorodiphenylsulfone with tris(4‐hydroxy phenyl)ethane were performed in DMSO with variation of feed ratio and concentration. For feed ratios of 1.0:1.3–1.0:1.5, soluble multicyclic poly(ether sulfone)s were obtained when the monomer concentration was below 0.05 M . The conversions were never complete under standard conditions, and doubling the reaction time yielded perfect multicyclic products free of endgroups; however, a small fraction of the product was crosslinked under these conditions. Quite similar results were obtained with 4,4′‐dichlorodiphenylsulfone at higher temperatures. When K2CO3 was replaced by tertiary amines, conversions and molecular weights were lower. The multicyclic poly(ether sulfone)s were characterized by MALDI‐TOF mass spectrometry, SEC, and DSC measurements. Broad molecular weight distributions with polydispersities in the range of 2.4–3.9 were found, and, surprisingly, two glass transitions were detectable in the DSC heating curves.
Biodegradable multiblock (co)polymers based on N‐(2‐hydroxypropyl)methacrylamide (HPMA) for drug delivery applications are prepared by azide–alkyne polycycloaddition of end‐functionalized precursors synthesized by reversible addition–fragmentation chain transfer polymerization. Copper‐catalyzed polyaddition of the heterotelechelic polymer precursors containing azide and alkyne groups provides (A)x‐type multiblock (co)polymers. For the first time, thermally degradable multiblock polymers of (AB)x‐type are prepared via polyaddition of homotelechelic polymer diazides with azo‐compounds containing two alkyne groups. A novel type of HPMA‐based multiblock (co)polymers undergoing the pH‐dependent hydrolysis is reported. The (co)polymers containing the Asp‐Pro‐Lys sequence are relatively stable in an aqueous buffer at physiological pH 7.4; however, they undergo rapid hydrolysis at pH 5.0 corresponding to the pH in lysosomes. The multiblock polymer containing the Gly‐Phe‐Leu‐Lys linkage is degraded in the presence of the lysosomal protease cathepsin B. Thermal degradation of the (AB)x‐type multiblock polymers proceeds even at 37 °C, yielding a mixture of polymer degradation products with molecular weights below the renal threshold.
Summary: Linear, three‐ and four‐armed block copolymers based on PEG and PSA were synthesized by melt polycondensation reactions. The CMC of the copolymer was measured using the dye solubilization method. The copolymers were found to self‐aggregate in water to form micelles above the CMC. The micellar solutions were prepared with different methods and investigated by DLS and AFM. The DLS method was used to measure the mean hydrodynamic diameters of the micelles. It was found that preparation method and condition of the micellar solution, as well as the structure and composition of the copolymer had effects on the hydrodynamic diameter of the copolymer micelles. AFM studies showed that the morphology of the micelle was spherical.
Synthesis of 3‐armed stars based on poly(ethylene glycol) and poly(sebacic anhydride). 相似文献
Size exclusion chromatography coupled with light scattering (SEC/MALS), dynamic light scattering (DLS), steady‐state and time‐resolved fluorescence, as well as molecular dynamics (MD) simulations are used to study the behavior of several poly(ethylene glycol) (PEG)/α‐cyclodextrins (αCDs) polyrotaxanes (PRs) in solution. The number of CD units in any of the PRs studied is always smaller than that required to saturate the PEG chains. These PRs seem to aggregate in dimethyl sulfoxide (DMSO) solution. The presence of hairpins in the non‐saturated PRs contributes to diminishing their expected large dimensions. Intra‐ and intermolecular interactions and forces responsible for hairpins and aggregation are investigated.
The layer‐by‐layer (LbL) assembly technique was applied for the surface modification of biodegradable poly(lactide‐co‐glycolide) nanoparticles (NPs), employing poly(acrylic acid) (PAA), and polyethylenimine (PEI) as building blocks. Amino terminated poly(ethylene glycol) (PEG) and folate decorated PEG (PEG‐FA) were grafted onto the multilayers via condensation between carboxylic groups and amine groups from PEG or PEG‐FA. The LbL assembly and the covalent functionalization were monitored by means of ζ‐potential measurements and the quartz crystal microbalance with dissipation technique (QCM‐D). Protein adsorption after incubation of the NPs in culture medium containing optionally the serum proteins was investigated and related to cellular uptake. Experiments on cellular uptake showed that after PEGylation the uptake ratio of the NPs decreased significantly, but became three times larger when PEG‐FA was grafted on the NPs instead of the PEG.
The amphiphilic triblock copolymer PLA‐b‐PLL‐b‐MPEG is prepared in three steps through acylation coupling between the terminal amino groups of PLA‐b‐PZLL‐NH2 and carboxyl‐terminal MPEG, followed by the deprotection of amines. The block copolymers are characterized via FT‐IR, 1H NMR, DSC, GPC, and TEM. TEM analysis shows that the triblock polymers can form polymeric micelles in aqueous solution with a homogeneous spherical morphology. The cytotoxicity assay indicates that the final triblock polymer micelles after deprotection show low cytotoxicity against Bel7402 human hepatoma cells. MPEG and PLL were introduced into the main chain of PLA affording a kind of ideal bioabsorbable polymer materials, which is expected to be useful in drug and gene delivery.
A series of amphiphilic graft copolymers of poly(ethylene glycol)‐co‐glycidol‐graft‐(ε‐caprolactone) (PEG‐co‐PGL‐g‐PCL) with PEG as the hydrophilic backbone chain and hydrophobic PCL as side chains have been synthesized by living anionic polymerization and ring‐opening polymerization. By changing the composition of the PEG‐co‐PGL backbone chains, and the molar ratio of CL monomer to PEG‐co‐PGL in the feed, copolymers with well‐defined architecture and controllable numbers and length of graft chains can be obtained. The micellization and drug release of the PEG‐co‐PGL‐g‐PCL graft copolymers have been studied in terms of dependence on graft numbers and length, and the results indicate that the micelles with shorter PCL side chains have more compact cores and a relatively small size which are favorable for drug loading and controlled release.
A new poly(3‐butylthiophene) derivative with one terminus functionalized with a 1H,1H,2H,2H,3H,3H‐perfluoroundecyl group (P3BT‐F17) is synthesized by Ni‐catalyzed quasi‐living polymerization and the subsequent quenching of living ends by allyl‐Grignard reagent and the attachment of a fluoroalkyl chain. The quantitative introduction of fluoroalkyl chain ends is confirmed by matrix‐assisted laser desorption/ionization time‐of‐flight–mass spectrometry (MALDI‐TOF‐MS), gel‐permeation chromatography (GPC), 1H NMR spectroscopy, and X‐ray photoelectron spectroscopy (XPS). The electronic properties of P3BT‐F17 in solution and its crystalline structure in the solid state are investigated by UV–vis spectroscopy and cyclic voltammetry (CV), and by DSC and X‐ray diffraction (XRD) analyses.
Reductively degradable multiblock polymers for gene and drug delivery were synthesised by oxidative polycondensation of poly(ethylene glycol)‐cysteine derivatives containing ester or urethane bonds. Hydrolysis of the polymers at pH = 5.5, 7.4 and 8.0 and reductive degradation with glutathione and dithiothreitol were studied. The hydrolysis rate of polymer esters increased with increase in pH; the hydrolysis of polymer urethanes was negligible. Chemical substitution of the pendant COOH or NH2 groups significantly affected the rate of the polymer degradation. Surface modification of poly(L ‐lysine)‐DNA complexes with PEG‐cystine multiblocks led to the formation of reductively degradable nanoparticles.
A variety of differently structured PEG‐based polymers can form physically cross‐linked PEG hydrogels with α‐cyclodextrin. The polymer structures strongly influence the properties of the hydrogel and its formation. Four different copolymers of methoxy PEG methacrylate and methacrylic acid are used together with α‐cyclodextrin to study hydrogel formation speed and gel strength. The hydrogels are formed within 1–25 min, and the formation process is examined in situ by dynamic light scattering. The gel formation time is pH dependent due to the methacrylic acid present in the polymers. The gel strength examined by texture analyzer also depends on the composition and pH. With prior mechanical destruction, all hydrogels are dissolvable in an excess of water, being a useful feature for an in vivo usage. By analyzing the structures of the hydrogels with confocal light microscopy (laser scanning confocal microscopy) and scanning electron microscope (SEM) after freeze etching, the different hydrogel structures can be observed. 相似文献
Summary: A new poly(ethylene glycol) derivative, 3‐[methoxypoly(oxyethylene)]methylene furan, I , was prepared from the reaction of 3‐furanmethanol with the mesylate of methoxypoly(oxyethylene) in tetrahydrofuran. The degree of end‐group conversion, as determined by NMR spectroscopy, was 100%. The Diels–Alder reactions of I with N‐phenylmaleimide, N‐glycinylmaleimide, maleic anhydride, N,N′‐hexamethylene bismaleimide, and diethyl acetylenedicarboxylate resulted in the corresponding adducts. For the adduct derived from I and N‐phenylmaleimide, its thermal reversible character was confirmed by applying a retro‐Diels–Alder reaction in the presence of a large excess of 2‐methylfuran, which restored the initial polymer I quantitatively. The adduct obtained from I and N‐glycinylmaleimide was converted into its succinimidyl ester and its hydrolysis rate in phosphate buffer (pH = 8) was determined. The reactivity of the adduct derived from I and N,N′‐hexamethylene bismaleimide with benzyl mercaptan was also investigated.
Multiarm PEO star polymers with a purely aliphatic polyether structure have been synthesized using hyperbranched polyglycerol (PG) with different molecular weights as a multifunctional initiator. Different degrees of deprotonation of the initiator were studied with respect to molecular weight control. The results show that the degree of deprotonation is a crucial parameter for the synthesis of well‐defined polymers with controlled molecular weights. Partial deprotonation of the PG hydroxyl groups (5–8%) was proven to represent an optimum for the synthesis of star polymers with molecular masses close to the theoretical values. Molecular weights of the stars ranged between 9 000 and 30 000 g · mol?1. MALDI‐ToF spectra confirmed that the PEO arms in the star polymers possess homogeneous lengths.
Well‐defined amphiphilic diblock copolymers of poly(N‐(2‐hydroxypropyl)methacrylamide)‐block‐poly(benzyl methacrylate) (PHPMA‐b‐PBnMA) are synthesized using reversible addition–fragmentation chain transfer polymerization. The terminal dithiobenzoate groups are converted into carboxylic acids. The copolymers self‐assemble into micelles with a PBnMA core and PHPMA shell. Their mean size is <30 nm, and can be regulated by the length of the hydrophilic chain. The compatibility between the hydrophobic segment and the drug doxorubicin (DOX) affords more interaction of the cores with DOX. Fluorescence spectra are used to determine the critical micelle concentration of the folate‐conjugated amphiphilic block copolymer. Dynamic light scattering measurements reveal the stability of the micelles with or without DOX. Drug release experiments show that the DOX‐loaded micelles are stable under simulated circulation conditions and the DOX can be quickly released under acidic endosome pH. 相似文献
Summary: Monofunctional poly(εCL) having one CH2OH and one CO2CH3 endgroup was prepared by SnOct2 + MeOH‐initiated polymerizations of εCL at 80 °C. The CH2OH endgroups were reacted with IPTES. In this way, poly(εCL) having one CO2CH3 and one TES endgroup was obtained. Poly(εCL) having two CH2OH endgroups were prepared by means of SnOct2 and Tetra EG or 1,4‐butanediol as coinitiators. The molecular weight distribution significantly broadened when the polymerization temperature increased from 80 to 120 °C. The OH endgroups were quantitatively functionalized by addition of IPTES. Star‐shaped poly(εCL)s having three or four OH endgroups were prepared with 1,1,1‐tris(hydroxymethyl)propane or pentaerythritol as coinitiators. All endgroups were modified with IPTES. The lengths of the poly(εCL) segments were varied via the monomer/coinitiator ratio. All functionalized oligomers were characterized by 1H NMR spectroscopy and MALDI‐TOF mass spectrometry. Preliminary studies of film formation and adhesive properties were performed.
MALDI‐TOF mass spectrum of a poly(εCL) initiated with Sn(Oct)2 and 1,4‐butanediol and functionalized with IPTES. 相似文献
Chemically crosslinked hydrogels are prepared at remarkably low macromonomer concentrations from 8‐arm poly(ethylene glycol)‐poly(L ‐lactide) star block copolymers bearing acrylate end groups (PEG‐(PLLAn)8‐AC, n = 4 or 12) and multifunctional PEG thiols (PEG‐(SH)n, n = 2, 4, or 8) through a Michael‐type addition reaction. Hydrogels are obtained within 1 min after mixing PEG‐(PLLA4)8 ‐AC and PEG‐(SH)8 in phosphate buffered saline, quickly reaching a high storage modulus of 17 kPa. Lysozyme and albumin are released for 4 weeks from PEG‐(PLLA12)8‐AC/PEG‐(SH)8 hydrogels. Lysozyme release from PEG‐(PLLA12)8‐AC/PEG‐(SH)2 and PEG‐(PLLA12)8‐AC/PEG‐(SH)4 hydrogels is significantly faster with complete release in 3 and 12 d, respectively, as a result of a combination of degradation and diffusion. 相似文献
Magnetite nanoparticles are synthesized and functionalized with vinyl groups (by silanization reaction with VTMS) and further coated with poly(ethylene glycol) dithiol under UV activation via thiol‐ene addition. TEM analysis is in a good agreement with DLS analyses and shows that by vinyl functionalization and following PEG coating it was possible to achieve nanometer‐sized particles with an average size of about 20–50 nm, well distributed and not‐aggregated. Superparamagnetic‐like behavior of coated Fe3O4 nanoparticles, which is typically looked for in biomedical applications, is ensured by the Brownian motion of the magnetic NPs in the ferrofluid. The polymeric coating does not modify the magnetic response of the magnetite nanoparticles.
Poly[(R )‐3‐hydroxybutyrate] (P3HB) is a potential candidate for biomaterials due to its biocompatibility and biodegradability. However, P3HB needs to have tunable hydrophobicity, modification through chemical functionalization and the right hydrolytic stability to increase their potential for water‐based biomedical applications such as using them as in situ forming gels for drug delivery. This work focuses on using a copolymer, poly[(R )‐3‐hydroxybutyrate‐co‐4‐hydroxybutyrate] (P3HB4HB) in a thermogelling multiblock system with polypropylene glycol and polyethylene glycol to study the effect of the hydrophobic P3HB4HB on gelation properties, degradation, and drug release rates with reference to P3HB. Thermogels containing P3HB4HB segments show lower critical micellization concentration values in a range from 3 × 10−4 to 1.08 × 10−3 g mL−1 and lower critical gelation concentration values ranging from 2 to 6 wt% than that of gels containing P3HB. Furthermore, gels containing P3HB4HB degrade at a slower rate than the gels containing P3HB. Drug release studies of 5 µg mL−1 of doxorubicin show that gels containing P3HB4HB exhibit sustained release although the release rates are faster than gels containing P3HB. However, this can be modified by varying the concentration of the gels used. Process optimization of purifying the starting material is one important factor before the synthesis of these biomaterials.
The effect of thermal treatment on the transition of molecular packing and orientation of the semiconducting poly(2,5‐dihexyloxy‐p‐phenylene) (PPP) film is probed by the combination of in situ 2D grazing incidence X‐ray diffraction (2D GIXD) and selected area electron diffraction (SAED). The structure analysis indicates that PPP crystallizes in an orthorhombic unit cell with a = 21.20 Å, b = 3.78 Å, and c = 4.24 Å. A variation of the annealing temperature from 80 °C to 100 °C demonstrates that the worm‐like morphology in the pristine film melts and develops into nanowires. Furthermore, the molecular orientation transforms from face‐on to edge‐on via thermal annealing. Remarkably, a previously unknown metastable state of “slope” edge‐on with a tilt angle of 51.1° is observed. This orientation change arises from the heterogeneous nucleation and growth of edge‐on PPP crystal during crystallization from the melt.
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