Injectable supramolecular hybrid hydrogels formed by MWNT‐grafted‐poly(ethylene glycol) and α‐cyclodextrin

Poly(ethylene glycol)‐grafted‐multiwalled carbon nanotube (MWNT‐g‐PEG) was synthesized by a coupling reaction and formed inclusion complexes (ICs) after selective threading of the PEG segment of the MWNT‐g‐PEG through the cavities of α‐cyclodextrins (α‐CDs) units. The polypseudorotaxane structures of the as‐obtained hydrogels were confirmed by ¹H NMR, X‐ray diffraction and DSC analyses. The complexation of the PEG segments with α‐CDs and the hydrophobic interaction between the MWNT resulted in the formation of supramolecular hybrid hydrogels with a strong network. Thermal analysis showed that the thermal stability of the hydrogel was substantially improved by up to 100 °C higher than that of native hydrogel. The resultant hybrid hydrogels were found to be thixotropic and reversible, and could be applied as a promising injectable drug delivery system. The mechanical strength of the hybrid hydrogels was greatly improved in comparison with that of the corresponding native hydrogels. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3145–3151, 2010     

Preparation and characterization of macroporous poly(N‐isopropylacrylamide) hydrogels for the controlled release of proteins

Macroporous, temperature‐sensitive poly(N‐isopropylacrylamide) (PNIPAAm) hydrogels were synthesized with poly(ethylene glycol)s (PEGs; molecular weight = 2000–6000) as the pore‐forming agents. The influence of the molecular weight and PEG content on the responsive kinetics of these macroporous hydrogels was investigated. The PEG‐modified PNIPAAm hydrogels were characterized by the swelling ratio, deswelling–reswelling kinetics, Fourier transform infrared, and differential scanning calorimetry. The morphology of these hydrogels was analyzed with scanning electron microscopy. The prepared macroporous hydrogels exhibited some unique properties in comparison with the gels with low molecular weight PEGs (molecular weight < 2000) as the pore‐forming agents. In addition, a preliminary study on the controlled release of bovine serum albumin from these macroporous hydrogels was carried out. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 152–159, 2003     

Poly(ethylene glycol)–poly(L‐lactide) star block copolymer hydrogels crosslinked by metal–ligand coordination

The aqueous solution behavior and thermoreversible gelation properties of pyridine‐end‐functionalized poly(ethylene glycol)–poly(L ‐lactide) (PEG–(PLLA)₈–py) star block copolymers in the presence of coordinating transition metal ions were studied. In aqueous solutions, the macromonomers self‐assembled into micelles and micellar aggregates at low concentrations and formed physically crosslinked, thermoreversible hydrogels above a critical gel concentration (CGC) of 8% w/v. In the presence of transition metal ions like Cu(II), Co(II), or Mn(II), the aggregate dimensions increased. Above the CGC, the gel–sol transition shifted to higher temperatures due to the formation of additional crosslinks from intermolecular coordination complexes between metal ions and pyridine ligands. Furthermore, as an example, PEG–(PLLA)₈–py hydrogels stabilized by Mn(II)–pyridine coordination complexes were more resistant against degradation/dissolution when placed in phosphate buffered saline at 37 °C when compared with hydrogels prepared in water. Importantly, the stabilizing effect of metal–ligand coordination was noticeable at very low Cu(II) concentrations, which have been reported to be noncytotoxic for fibroblasts in vitro. These novel PEG–(PLLA)₈–py metallo‐hydrogels, which are the first systems to combine metal–ligand coordination with the advantageous properties of PEG–PLLA copolymer hydrogels, are appealing materials that may find use in biomedical as well as environmental applications like the removal of heavy metal ions from waste streams. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Antibacterial poly(ethylene glycol) hydrogels from combined epoxy‐amine and thiol‐ene click reaction

Antibacterial hydrogels containing quaternary ammonium (QA) groups were prepared via a facile thiol‐ene “click” reaction using multifunctional poly(ethylene glycol) (PEG). The multifunctional PEG polymers were prepared by an epoxy‐amine ring opening reaction. The chemical and physical properties of the hydrogels could be tuned with different crosslinking structures and crosslinking densities. The antibacterial hydrogel structures prepared from PEG Pendant QA were less well‐defined than those from PEG Chain‐End QA. Furthermore, functionalization of the PEG‐type hydrogels with QA groups produced strong antibacterial abilities against Staphylococcus aureus, and therefore has the potential to be used as an anti‐infective material for biomedical devices. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 656–667     

Dual‐responsive supramolecular inclusion complexes of block copolymer poly(ethylene glycol)‐block‐poly[(2‐dimethylamino)ethyl methacrylate] with α‐cyclodextrin

A new class of temperature and pH dual‐responsive and injectable supramolecular hydrogel was developed, which was formed from block copolymer poly(ethylene glycol)‐block‐poly[(2‐dimethylamino)ethyl methacrylate] (PEG‐b‐PDMAEMA) and α‐cyclodextrin (α‐CD) inclusion complexes (ICs). The PEG‐b‐PDMAEMA diblock copolymers with different ratio of ethylene glycol (EG) to (2‐dimethylamino)ethyl methacrylate (DMAEMA) (102:46 and 102:96, respectively) were prepared by atom transfer radical polymerization (ATRP). ¹H NMR measurement indicated that the ratio of EG unit to α‐CD in the resulted ICs was higher than 2:1. Thermal analysis showed that thermal stability of ICs was improved. The rheology studies showed that the hydrogels were temperature and pH sensitive. Moreover, the hydrogels were thixotropic and reversible. The self‐assembly morphologies of the ICs in different pH and ionic strength environment were studied by transmission electron microscopy. The formed biocompatible micelles have potential applications as biomedical and stimulus‐responsive material. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2143–2153, 2010     

Physical properties of glycosaminoglycan hydrogels

The chemical composition of glycosaminoglycan (GAG) hydrogels was found to have a profound effect on the physical properties of gels. Hyaluronan (HA) and chondroitin sulfate (CS) were each modified with adipic dihydrazide (ADH) with carbodiimide chemistry. The resulting polymer was crosslinked with various concentrations of poly(ethylene glycol) dialdehyde (PEG‐diald) to produce a series of hydrogels. The physical properties of these GAG hydrogels varied in a concentration‐dependent fashion. Maximal crosslinking was observed at a theoretical crosslinking of 50% for the HA‐ADH‐PEG‐diald hydrogels and 75% for the CS‐ADH‐PEG‐diald hydrogels. Adding PEG‐diald beyond the optimum for crosslinking prolonged the in vitro enzymatic degradation time of the hydrogels. The swelling of the crosslinked GAG hydrogels was correlated with the amount of PEG‐diald used rather than with the crosslinking density. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 4344–4356, 2004     

Sol–gel transition behavior of biodegradable three‐arm and four‐arm star‐shaped PLGA–PEG block copolymer aqueous solution

Two types of temperature‐sensitive biodegradable three‐arm and four‐arm star‐shaped poly(DL ‐lactic acid‐co‐glycolic acid‐b‐ethylene glycol) (3‐arm and 4‐arm PLGA–PEG) were successfully synthesized via the coupling reaction of 3‐arm and 4‐arm PLGA and α‐monocarboxyl‐ω‐monomethoxypoly(ethylene glycol) (CMPEG). In dilute aqueous solutions, star PLGA–PEGs showed the temperature‐ and concentration‐dependent formation and aggregation of micelles over specific concentration and specific temperature. With increasing the molecular weight and the relative hydrophobicity of hydrophobic PLGA block, critical micelle temperature (CMT) decreased. Aqueous solution of 4‐arm PLGA–PEG started to form micelles at lower temperature and showed sharper temperature‐dependent growth in micelle size. These results are due to the enhanced hydrophobicity of PLGA block. On the other hand, at high concentration, two types of 3‐arm and 4‐arm PLGA–PEG showed sol–gel–sol transition behavior as the temperature was increased. The 3‐arm and 4‐arm PLGA–PEG showed sol–gel transition at higher polymer concentrations (above 24 wt %) than the PEG–PLGA–PEG triblock copolymer. As the molecular weight and the relative hydrophobicity of PLGA block increased, the critical gel concentration (CGC) decreased. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 888–899, 2006     

Pendant groups fine‐tuning thermal gelation of poly(ε‐caprolactone)‐b‐poly(ethylene glycol)‐b‐poly(ε‐caprolactone) aqueous solution

Novel poly(ε‐caprolactone)‐b‐poly(ethylene glycol)‐b‐poly(ε‐caprolactone) (PCL‐PEG‐PCL) bearing pendant hydrophobic γ‐(carbamic acid benzyl ester) groups (PECB) and hydrophiphilic amino groups (PECN) were synthesized based on the functionalized comonomer γ‐(carbamic acid benzyl ester)‐ε‐caprolactone (CABCL). The thermal gelation behavior of the amphiphilic copolymer aqueous solutions was examined. The phase transition behavior could be finely tuned via the pendant groups, and an abnormal phenomenon occurred that the sol–gel transition temperature shifted to a higher temperature for PECB whereas a lower temperature for PECN. The micelles percolation was adopted to clarify the hydrogel mechanism, and the effect of the pendant groups on the micellization was further investigated in detail. The results demonstrated that the introduction of γ‐(carbamic acid benzyl ester) pendant groups significantly decreased the crystallinity of the copolymer micelles whereas amino pendant groups made the micelles easy to aggregate. Thus, the thermal gelation of PEG/PCL aqueous solution could be finely tuned by the pendant groups, and the pendant groups modified PEG/PCL hydrogels are expected to have great potential biomedical application. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 2571–2581     

Theoretical and experimental characterization of amino‐PEG‐phosphonate‐terminated Polyphosphorhydrazone dendrimers: Influence of size and PEG capping on cytotoxicity profiles

The synthesis of new series of PPH (poly(phosphorhydrazone)) dendrimers with amino‐PEG phosphonates or the corresponding amino‐PEG phosphonic acids as terminal groups is presented, from generations 1–3. The size of PEG‐terminated dendrimers is experimentally measured by diffusional NMR, and by means of dynamic light scattering. Classical molecular dynamics and well‐tempered metadynamics simulations are used to assess or confirm the formation of aggregates in some cases. The influence of PEG capping on the cytotoxicity profiles of the dendrimers is evaluated on human peripheral blood mononuclear cells by means of LIVE/DEAD assays, and confirms the importance of PEG capping to ensure low cytotoxicity. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 761–774     

Synthesis and characterization of thermoresponsive poly(ethylene glycol)‐based hydrogels and their magnetic nanocomposites

Temperature‐responsive hydrogels are one of the most widely studied types of stimuli‐responsive hydrogel systems. Their ability to transition between their swollen and collapsed states makes them attractive for controlled drug delivery, microfluidic devices, and biosensor applications. Recent work has shown that poly(ethylene glycol) (PEG) methacrylate polymers are temperature‐responsive and exhibit a wide range of lower critical solution temperatures based on the length of ethylene glycol units in the macromer chain. The addition of iron oxide nanoparticles into the hydrogel matrix can provide the ability to remotely heat the gels upon exposure to an alternating magnetic field (AMF). In this work, diethylene glycol (n = 2) methyl ether methacrylate and PEG (n = 4.5) methyl ether methacrylate copolymers were polymerized into hydrogels with 5 mol % PEG 600 (n = 13.6) dimethacrylate as the crosslinker along with 5 wt % iron oxide nanoparticles. Volumetric swelling studies were completed from 22 to 80 °C and confirmed the temperature‐responsive nature of the hydrogel systems. The ability of the gels to collapse in response to rapid temperature changes when exposed to an AMF was demonstrated showing their potential use in biomedical applications such as controlled drug delivery and hyperthermia therapy. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3229–3235, 2010     

pH‐responsive ionic poly(N,N‐diethylaminoethyl methacrylate‐co‐N‐vinyl‐2‐pyrrolidone) hydrogels: Synthesis and swelling properties

A series of an ionic hydrogels composed of N,N‐diethylaminoethyl methacrylamide (DEAEMA), N‐vinyl‐2‐pyrrolidone (VP), and itaconic acid were synthesized by free‐radical cross‐linking copolymerization in water–ethanol mixture by using N,N‐methylenebis(acrylamide) as the cross‐linker, ammonium persulfate as the initiator, and N,N,N′,N′‐tetramethylenediamine as the activator. The swelling behaviors of these hydrogels were analyzed in buffer solutions at various pH. It was observed that the swelling behavior of cross‐linked ionic poly(N,N‐diethylaminoethyl methacrylamide‐co‐N‐vinyl‐2‐pyrrolidone) [P(DEAEMA/VP)] hydrogels at different pH agreed with the modified Flory–Rehner equation based on the affine network model and the ideal Donnan theory. The swelling process in buffer solutions at various pH was found to be Fickian‐type diffusion. The pH‐reversibility and on–off switching properties of the P(DEAEMA/VP) hydrogels may be considered as good candidate to design novel drug‐delivery system. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 2819–2828, 2005     

FT‐IR characterization and hydrolysis of PLA‐PEG‐PLA based copolyester hydrogels with short PLA segments and a cytocompatibility study

A series of the biodegradable copolyester hydrogels was prepared using a redox‐initiated polymerization with a constant 1:9 mole ratio of the Boltorn‐based acrylate and diacrylate triblock comacromonomers. The Boltorn® macromonomer was derived from the hyperbranched polyester Boltorn H20, which was functionalized at each terminus with poly(ethylene glycol) acrylate, and the diacrylate triblock macromonomer was poly (lactide‐b‐ethylene glycol‐b‐lactide) diacrylate. The hydrolysis of the copolyesters at pH 7.4 in a phosphate buffered saline solution at 37 °C was studied using ATR‐FTIR spectroscopy. It was found that the presence of the Boltorn, the PEG, and lactide block lengths both play vital roles in determining the structure‐property relationships in these materials. The ATR‐FTIR studies showed that with increasing lactide segment length, the rate of ester hydrolysis increased due to the increased concentration of the hydrolytically sensitive poly(lactic acid) (PLA) ester groups in the network. However, incorporation of Boltorn into the PLA‐PEG‐PLA copolymer did not significantly change the kinetic rate constant for hydrolysis of the PLA segments. The cytocompatibility of a typical one of these materials in the presence of its degradation by‐products was assessed using cultured osteoblasts from the rat. The hydrogel was degraded for 28 days and found to be cytocompatible with osteoblasts over days 23 to 28 of the hydrolysis period. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 5163–5176     

RAFT synthesis of a water‐soluble triblock copolymer of poly(styrenesulfonate)‐b‐poly(ethylene glycol)‐b‐poly(styrenesulfonate) using a macromolecular chain transfer agent in aqueous solution

Triblock copolymers of poly(styrenesulfonate)‐b‐poly(ethylene glycol)‐b‐poly(styrenesulfonate) with narrow molecular weight distribution (M_w/M_n = 1.28–1.40) and well‐defined structure have been synthesized in aqueous solution at 70 °C via reversible addition‐fragmentation chain transfer polymerization. Poly(ethylene glycol) (PEG) capped with 4‐cyanopentanoic acid dithiobenzoate end groups was used as the macro chain transfer agent (PEG macro‐CTA) for sole monomer sodium 4‐styrenesulfonate. The reaction was controllable and displayed living polymerization characteristics and the triblock copolymer had designed molecular weight. The reaction rate depended strongly on the CTA and initiator concentration ratio [CTA]₀/[ACPA]₀: an increase in [CTA]₀/[ACPA]₀ from 1.0 to 5.0 slowed down the polymerization rate and improved the molecular weight distribution with a prolonged induction time. The polymerization proceeded, following first‐order kinetics when [CTA]₀/[ACPA]₀ = 2.5 and 5.0. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3698–3706, 2007     

Multiphysical modeling and meshless simulation of electric‐sensitive hydrogels

According to a multiphase mixture theory, we have mathematically developed a multiphysical model with chemoelectromechanical coupling considerations, termed the multieffect‐coupling electric‐stimulus (MECe) model, to simulate the responsive behavior of electric‐sensitive hydrogels immersed in a bath solution under an externally applied electric field. For solutions of the MECe model consisting of coupled nonlinear partial differential governing equations, a meshless Hermite–Cloud method with a hierarchical iteration technique has been used for a one‐dimensional steady‐state analysis of a hydrogel strip. The computed results are compared with the experimental data, and there is very good agreement. Simulations within the domains of both hydrogels and surrounding solutions also present distributions of the ionic concentrations and electric potential as well as the hydrogel displacement. The effects of various physical parameters on the response behavior of electric‐stimulus responsive hydrogels are discussed in detail. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 1514–1531, 2004     

Side‐chain crystallization behavior of graft copolymers consisting of an amorphous main chain and crystalline side chains. II. Poly(n‐hexyl methacrylate)‐graft‐poly(ethylene glycol)

The phase behavior and crystallization of graft copolymers consisting of poly(n‐hexyl methacrylate) (PHMA) as an amorphous main chain and poly(ethylene glycol) (PEG) as crystallizable side chains (HMAx with 15 ≤ x ≤ 73, where x represents the weight percentage of PEG) were investigated. Small‐angle X‐ray scattering profiles measured above the melting temperature of PEG suggested that a microdomain structure with segregated PHMA and PEG domains was formed in HMA40 and HMA46. This phase behavior was qualitatively described by a calculated phase diagram based on the mean‐field theory. Because of the segregation of PEG into microdomains, the crystallization temperature of the PEG side chains in HMAx was higher than that in poly(methyl acrylate)‐graft‐poly(ethylene glycol) having a similar value of x, which was considered to be in a disordered state above the melting temperature. In HMAx with x ≤ 40, PEG crystallization was strongly restricted, probably because the PEG microdomains were isolated in the PHMA matrix. As a result, the growth of PEG spherulite was not observed because the PEG crystallization occurred after vitrification of the PHMA segregated domains. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 129–137, 2007     

Release of theophylline and aminophylline from acrylic acid/n‐alkyl methacrylate hydrogels

The swelling capacity and release rate of two homologous drugs, theophylline and aminophylline, from acrylic acid/n‐alkyl methacrylate hydrogels have been studied. The maximum equilibrium swelling increases as the molar fraction of acrylic acid or the chain length of the methacrylate in the hydrogels increases. Water diffusion to the hydrogels is non‐Fickian. Both drugs are released from the fully swollen hydrogels according to Fick's law. However, the drug release from xerogels deviates from Fick's law, especially for aminophylline. As expected because of its larger size, aminophylline diffuses more slowly than theophylline under similar experimental conditions. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2756–2765, 2004     

Synthesis of star polymers via nitroxide mediated free‐radical polymerization: A “core‐first” approach using resorcinarene‐based alkoxyamine initiators

The synthesis of new octafunctional alkoxyamine initiators for nitroxide‐mediated radical polymerization (NMRP), by the derivatization of resorcinarene with nitroxide free radicals viz TEMPO and a freshly prepared phosphonylated nitroxide, is described. The efficiency of these initiators toward the controlled radical polymerization of styrene and tert‐butyl acrylate is investigated in detail. Linear analogues of these multifunctional initiators were also prepared to compare and evaluate their initiation efficiency. The favorable conditions for polymerization were optimized by varying the concentration of initiators and free nitroxides, reaction conditions, etc., to obtain well‐defined star polymers. Star polystyrene thus obtained were further used as macro‐initiator for the block copolymerization with tert‐butyl acrylate. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5559–5572, 2007     

Synthesis,characterization, and crosslinking of methacrylate‐telechelic PDMAAm‐b‐PDMS‐b‐PDMAAm copolymers

The synthesis and molecular characterization of a new amphiphilic conetwork (APCN) designed for silicone hydrogel use is described. The synthesis strategy, outlined in Scheme 1 , calls for the preparation, by the RAFT technique, of a new methacrylate‐telechelic amphiphilic pentablock, MA‐PHEA‐b‐PDMAAM‐b‐PDMS‐b‐PDMAAm‐b‐PHEA‐MA, and its crosslinking to the target APCN. The sketch shows the architecture of the APCN (dotted lines, PDMAAm; solid lines, PDMS; clusters, MA‐based crosslinking sites; see Fig. 3 ). All six synthesis steps proceed smoothly and efficiently, and the products are optically clear, colorless membranes exhibiting properties appropriate for ophthalmic use. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4284–4290, 2007     

Synthesis and characterization of novel amphiphilic block copolymers di‐, tri‐, multi‐, and star blocks of PEG and PIB

A simple but efficient strategy has been developed for the synthesis of novel di‐, tri‐, multi‐, and star‐block copolymers comprising poly(ethylene glycol) (PEG) and polyisobutylene (PIB) blocks. The synthesis principle involves the coupling of appropriately terminally functionalized PEG and PIB sequences, specifically the hydrosilation of mono‐, di‐, and tetra‐allyl‐telechelic PEGs (PEG‐allyl, allyl‐PEG‐allyl, and C(‐PEG‐allyl)₄ by mono‐ and di‐Si(CH₃)₂H telechelic PIBs (PIB‐SiH and HiS‐PIB‐SiH). Representative block copolymers, for example, PEG‐PIB, PIB‐PEG‐PIB, (‐PIB‐PEG‐)_n, and C(‐PEG‐PIB)₄ have been assembled and their structures determined by ¹H and ¹³C NMR spectroscopy. The bulk and surface morphology of select triblocks have been investigated by DSC and AFM and the findings interpreted in terms of phase‐separated PEG and PIB microdomains. The swelling behavior in water of various block copolymers also has been studied. Block copolymers containing 50–70 wt % PIB produce hydrogels, the integrity of which is maintained by physical crosslinks by PIB segments. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 3200–3209, 2000     

Self‐assembly of amphiphilic tris(2,2′‐bipyridine)ruthenium‐cored star‐shaped polymers

Amphiphilic tris(2,2′‐bipyridine)ruthenium‐cored star‐shaped polymers consisting of one polystyrene block and two poly(N‐isopropylacrylamide) blocks were prepared by the “arm‐first” method in which RAFT polymerization and nonconvalent ligand–metal complexation were employed. The prepared amphiphilic star‐shaped metallopolymers are able to form micelles in water. The size and distribution of the micelles were studied by dynamic light scattering and transmission electron microscopy techniques. Preliminary studies indicate that the polymer concentration and the hydrophilic poly(N‐isopropylacrylamide) block length can affect the morphologies of the formed metal‐interfaced core–shell micelles in water. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4204–4210, 2007