Preparation of interpenetrating polymer network composed of poly(ethylene glycol) and poly(acrylamide) hydrogels as a support of enzyme immobilization

Poly(ethylene glycol)(PEG)‐based interpenetrating polymeric network (IPN) hydrogels were prepared for the application of enzyme immobilization. Poly(acrylamide)(PAAm) was chosen as the other network of IPN hydrogel and different concentration of PAAm networks were incorporated inside the PEG hydrogel to improve the mechanical strength and provide functional groups that covalently bind the enzyme. Formation of IPN hydrogels was confirmed by observing the weight per cent gain of hydrogel after incorporation of PAAm network and by attenuated total reflectance/Fourier transform infrared (ATR/FTIR) analysis. Synthesis of IPN hydrogels with higher PAAm content produced more crosslinked hydrogels with lower water content (WC), smaller M_c and mesh size, which resulted in enhanced mechanical properties compared to the PEG hydrogel. The IPN hydrogels exhibited tensile strength between 0.2 and 1.2 MPa while retaining high levels of hydration (70–81% water). For enzyme immobilization, glucose oxidase (GOX) was immobilized to PEG and IPN hydrogel beads. Enzyme activity studies revealed that although all the hydrogels initially had similar enzymatic activity, enzyme‐immobilizing PEG hydrogels lost most of the enzymatic activity within 2 days due to enzyme leaching while IPN hydrogels maintained a maximum 80% of the initial enzymatic activity over a week due to the covalent linkage between the enzyme and amine groups of PAAm. Copyright © 2008 John Wiley & Sons, Ltd.     

Synthesis and characterization of poly(ethylene glycol)‐based thermo‐responsive polyurethane hydrogels for controlled drug release

The thermo‐responsiveness, swelling and mechanical properties of a series of novel poly(ester‐ether urethane) hydrogels have been investigated. These thermo‐sensitive hydrogels were obtained by combining hydrophobic biodegradable poly(ε‐caprolactone) diols and hydrophilic two‐, three‐ and four‐arm hydroxyl terminated poly(ethylene glycol) (PEG) of various molecular weights, using hexamethylene diisocyanate, dichloroethane as solvent and a tin‐based catalyst. The use of multifunctional PEGs leads to the formation of covalent crosslinking points allowing an additional control of the swelling capability. Thus, it was found that tuning the hydrophilic/hydrophobic balance and the crosslinking degree by changing the composition, the swelling and the thermo‐responsive behavior of these hydrogels could be modulated. The obtained hydrogels showed a volume transition at around room temperature. Therefore, and taking into account their biocompatibility, these hydrogels show promising properties for biomedical applications, such as drug delivery. Thus, the loading and release of diltiazem hydrochloride, an antihypertensive drug used as model, were investigated. These new PEG polyurethane hydrogels were able to incorporate a high amount of drug providing a sustained release after an initial burst effect. Copyright © 2013 John Wiley & Sons, Ltd.     

Photocrosslinked hydrogels based on copolymers of poly(ethylene glycol) and lysine

A group of new, water-soluble poly(ether-urethane)s, derived from poly(ethylene glycol) and the amino acid L -lysine, provide pendent carboxylic acid groups along the polymer backbone at regular intervals. The carboxylic acid groups were utilized for the attachment of acrylate and methacrylate pendent chains (hydroxyethyl acrylate, hydroxyethyl methacrylate, aminoethyl methacrylate, and aminoethyl methacrylamide), leading to functionalized polymers. The pendent chains were attached via ester and/or amide bonds having different degrees of hydrolytic stability. The attachment reactions proceeded with high yields (up to 95%). The functionalized polymers were subsequently photopolymerized (UV irradiation) to obtain crosslinked hydrogels. Crosslinked membranes with the highest degree of mechanical strength were obtained when the crosslinking reaction was performed in dioxane with benzoin methyl ether (0.1 wt %) as the initiator. the crystallinity, thermomechanical properties, and hydrolytic stability of the crosslinked membranes were studied. All membranes were transparent and highly swellable (equilibrium water content: 64–88%). The tensile strength in the swollen state ranged from 0.15 to 1.09 MPa. Under physiological conditions (phosphate buffered water, 0.1M, pH 7.4, 37°C) the hydrolytic stability of the hydrogels varied depending on the bonds used in the attachment of the acrylate pendent chains: Hydrogels with hydroxyethyl acrylate pendent chains dissolved within 30 days, while hydrogels containing aminoethyl methacrylamide pendent chains remained unchanged throughout a 30 day period. Using high molecular weight FITC-dextrans as model compounds, complete release from the swollen hydrogels required between 60 and 150 h. Overall, the evaluation of poly(ethylene glycol)-lysine derived, photocrosslinked hydrogels indicated that these materials provide a range of potentially useful properties. © 1994 John Wiley & Sons, Inc.     

Methoxy poly(ethylene glycol)‐b‐poly(octadecanoic anhydride)‐b‐methoxy poly(ethylene glycol) amphiphilic triblock copolymer nanoparticles as delivery vehicles for paclitaxel

A series of amphiphilic triblock copolymers, methoxy poly(ethylene glycol)‐b‐poly(octadecanoic anhydride)‐b‐methoxy poly(ethylene glycol) (mPEG‐b‐POA‐b‐mPEG), were prepared via melt polycondensation of methoxy poly(ethylene glycol) (mPEG) and poly(octadecanoic anhydride) (POA). mPEG‐b‐POA‐b‐mPEG were characterized by FTIR, ¹H‐NMR, GPC, DSC, and XRD. Drug‐loaded mPEG‐b‐POA‐b‐mPEG nanoparticles (NPs) with spherical morphology and narrow size polydispersity index were prepared by nanoprecipitation technique with paclitaxel as the model drug. In vitro release behaviors of drug‐loaded NPs present that the biphasic process and the release mechanism of each phase are zero order drug releases. According to this study, mPEG‐b‐POA‐b‐mPEG NPs could serve as suitable delivery agents for paclitaxel and other hydrophobic drugs. Copyright © 2009 John Wiley & Sons, Ltd.     

Gas‐forming poly(ethylene glycol)‐b‐poly(L‐lactic acid) micelles

In this study, a novel drug‐carrying micelle composed of methoxy poly(ethylene glycol) (mPEG)‐b‐poly(L‐lactic acid) (PLLA) with gas‐forming carbonate linkage was fabricated. Here, the gas‐forming carbonate linkage was formed by the chemical coupling of the terminal hydroxyl group of the PLLA block and benzyl chloroformate (BC). mPEG‐b‐PLLA‐BC was self‐organized in aqueous solution: the PEG block on the hydrophilic outer shell and the PLLA‐BC block in the hydrophoboic innor core. The cleavage of carbonate linkage by hydrolysis and formation of carbon dioxide nanobubbles in the micellar core enabled an accelerated release of the encapsulated anticancer drug (doxorubicin: DOX) from the mPEG‐b‐PLLA‐BC micelles. The amount of drug (DOX) released from the mPEG‐b‐PLLA‐BC micelle was higher than that from the conventional mPEG‐b‐PLLA micelle, which allowed for increased in vitro toxicity against KB tumor cells. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis and On‐Demand Gelation of Multifunctional Poly(ethylene glycol)‐Based Polymers

The synthesis of a novel photoreactive poly(ethylene glycol) (PEG)‐based polymer with caged carbonyl groups is reported. We further demonstrate its use for the on‐demand fabrication of hydrogels. For rapid gelation, a hydrazide‐functionalized PEG is used as the second component for the hydrogel preparation. The photoreactive PEG‐based polymer is designed for controlled cleavage of the protecting groups upon exposure to UV light releases free aldehyde moieties, which readily react with hydrazide groups in situ. This hydrogel system may find applications in controlled release drug delivery applications, when combined with in situ gelation. Furthermore, the possibility of forming gels specifically upon UV irradiation gives an opportunity for 3D fabrication of degradable scaffolds.

     

Injectable poly(ethylene glycol) hydrogels for sustained doxorubicin release

Water‐soluble poly(ethylene glycol) derivatives with multiple “clickable” mercapto groups or double bonds were facilely synthesized in a large scale by direct polycondensation of oligo(ethylene glycol) diol with mercaptosuccinic acid or maleic acid catalyzed by scandium trifluoromethanesulfonate under mild conditions. Injectable hydrogels containing doxorubicin hydrochloride (DOX · HCl) could be rapidly formed using these poly(ethylene glycol) derivatives as precursors via in situ thiol‐ene “click” reaction under physiological conditions without light, initiator, or metal catalyst. DOX · HCl could be sustained released from the hydrogels as a result of the hindrance of the three dimensional hydrogel network on the drug molecules, which makes this kind of DOX‐loaded hydrogels a promising candidate for localized tumor chemotherapy. Copyright © 2016 John Wiley & Sons, Ltd.     

Novel synthesis of biodegradable star poly(ethylene glycol)‐block‐poly(lactide) copolymers

Biodegradable star‐shaped poly(ethylene glycol)‐block‐poly(lactide) copolymers were synthesized by ring‐opening polymerization of lactide, using star poly(ethylene glycol) as an initiator and potassium hexamethyldisilazide as a catalyst. Polymerizations were carried out in toluene at room temperature. Two series of three‐ and four‐armed PEG‐PLA copolymers were synthesized and characterized by gel permeation chromatography (GPC) as well as ¹H and ¹³C NMR spectroscopy. The polymerization under the used conditions is very fast, yielding copolymers of controlled molecular weight and tailored molecular architecture. The chemical structure of the copolymers investigated by ¹H and ¹³C NMR indicates the formation of block copolymers. The monomodal profile of molecular weight distribution by GPC provided further evidence of controlled and defined star‐shaped copolymers as well as the absence of cyclic oligomeric species. The effects of copolymer composition and lactide stereochemistry on the physical properties were investigated by GPC and differential scanning calorimetry. For the same PLA chain length, the materials obtained in the case of linear copolymers are more viscous, whereas in the case of star copolymer, solid materials are obtained with reduction in their T_g and T_m temperatures. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3966–3974, 2007     

Synthesis of poly[N‐isopropylacrylamide‐g‐poly(ethylene glycol)] with a reactive group at the poly(ethylene glycol) end and its thermosensitive self‐assembling character

Poly[N‐isopropylacrylamide‐g‐poly(ethylene glycol)]s with a reactive group at the poly(ethylene glycol) (PEG) end were synthesized by the radical copolymerization of N‐isopropylacrylamide with a PEG macromonomer having an acetal group at one end and a methacryloyl group at the other chain end. The temperature dependence of the aqueous solutions of the obtained graft copolymers was estimated by light scattering measurements. The intensity of the light scattering from aqueous polymer solutions increased with increasing temperature. In particular, at temperatures above 40°C, the intensity abruptly increased, indicating a phase separation of the graft copolymer due to the lower critical solution temperature (LCST) of the poly(N‐isopropylacrylamide) segment. No turbidity was observed even above the LCST, and this suggested a nanoscale self‐assembling structure of the graft copolymer. The dynamic light scattering measurements confirmed that the size of the aggregate was in the range of several tens of nanometers. The acetal group at the end of the PEG graft chain was easily converted to the aldehyde group by an acid treatment, which was analyzed by ¹H NMR. Such a temperature‐induced nanosphere possessing reactive PEG tethered chains on the surface is promising for new nanobased biomedical materials. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 1457–1469, 2006     

Synthesis and non‐isothermal crystallization kinetics of poly(ethylene terephthalate)‐co‐poly(propylene glycol) copolymers

Poly(ethylene terephthalate)‐co‐poly(propylene glycol) (PET‐co‐PPG) copolymers with PPG ratio ranging from 0 to 0.90 mol% were synthesized by the melt copolycondensation. The intrinsic viscosity, structure, non‐isothermal crystallization behavior, nucleation and spherulitic growth of the copolymers were investigated by Ubbelohde viscometer, Proton Nuclear Magnetic Resonance (¹H‐NMR), differential scanning calorimetry, and polarized optical microscopy, respectively. The non‐isothermal crystallization process of the copolymers was analyzed by Avrami, Ozawa, Mo's, Kissinger, and Dobreva methods, respectively. The results showed that the crystallizability of PET was apparently enhanced with incorporating a small amount of PPG, which first rose and then reduced with increasing amount of PPG in the copolymers at a given cooling rate. The crystallization mechanism was a three‐dimensional growth with both instantaneous and sporadic nucleation. Particularly, PET‐co‐PPG containing 0.60 mol% PPG exhibited the highest crystallizability among all the copolymers. Copyright © 2015 John Wiley & Sons, Ltd.     

Biocompatibility evaluation of self‐assembled micelles prepared from poly(lactide‐co‐glycolide)‐poly(ethylene glycol) diblock copolymers

In this work, a series of PLGA‐PEG diblock copolymers were synthesized by ring‐opening polymerization of L‐lactide and glycolide using mPEG as macroinitiator and stannous octoate as catalyst. Spherical micelles were obtained from the various copolymers by using co‐solvent evaporation method. The biocompatibility of micelles was evaluated with the aim of assessing their potential in the development of drug delivery systems. Various aspects of biocompatibility were considered, including MTT assay, agar diffusion test, release of cytokines, hemolytic test, dynamic clotting time, protein adsorption in vitro, and zebrafish embryonic compatibility in vivo. The combined results revealed that the micelles present good cytocompatibility and hemocompatibility in vitro. Moreover, the cumulative effects of micelles throughout embryos developing stages have no toxicity in vivo. It is thus concluded that micelles prepared from PLGA‐PEG copolymers present good biocompatibility as potential drug carrier.     

Antimicrobial loading into and release from poly(ethylene glycol)/poly(acrylic acid) semi‐interpenetrating hydrogels

Electrostatic interactions within a semi‐interpenetrating network (semi‐IPN) gel can control the postsynthesis loading, long‐term retention, and subsequent release of small‐molecule cationic antibiotics. Here, electrostatic charge is introduced into an otherwise neutral gel [poly(ethylene glycol) (PEG)] by physically entrapping high‐molecular‐weight poly(acrylic acid) (PAA). The network structure is characterized by small‐angle neutron scattering. PEG/PAA semi‐IPN gels absorb over 40 times more antibiotic than PAA‐free PEG gels. Subsequent soaking in physiological buffer (pH 7.4; 0.15 M NaCl) releases the loaded antibiotics for periods as long as 30 days. The loaded gels elute antibiotics with diffusivities of 4.46 × 10^?8 cm²/s (amikacin) and 2.08 × 10^?8 cm²/s (colistin), which are two orders of magnitude less than those in pure PEG gels where diffusion is controlled purely by gel tortuosity. The release and hindered diffusion can be understood based on the partial shielding of the charged groups within the loaded gel, and they have a significant effect on the antimicrobial properties of these gels. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016 , 54, 64–72     

Drug release and biocompatibility of self‐assembled micelles prepared from poly (ɛ‐caprolactone/glycolide)‐poly (ethylene glycol) block copolymers

A series of poly(?‐caprolactone/glycolide)‐poly(ethylene glycol) (P(CL/GA)‐PEG) diblock copolymers were prepared by ring opening polymerization of a mixture of ?‐caprolactone and glycolide using mPEG as macro‐initiator and stannous octoate as catalyst. Self‐assembled micelles were prepared from the copolymers using nanoprecipitation method. The micelles were spherical in shape. The micelle size was larger for copolymers with longer PEG blocks. In contrast, the critical micelle concentration of copolymers increased with decreasing the overall hydrophobic block length. Drug loading and drug release studies were performed under in vitro conditions, using paclitaxel as a hydrophobic model drug. Higher drug loading was obtained for micelles with longer poly(ε‐caprolactone) blocks. Faster drug release was obtained for micelles of mPEG2000 initiated copolymers than those of mPEG5000 initiated ones. Higher GA content in the copolymers led to faster drug release. Moreover, drug release rate was enhanced in the presence of lipase from Pseudomonas sp., indicating that drug release is facilitated by copolymer degradation. The biocompatibility of copolymers was evaluated from hemolysis, dynamic clotting time, and plasma recalcification time tests, as well as MTT assay and agar diffusion test. Data showed that copolymer micelles present outstanding hemocompatibility and cytocompatibility, thus suggesting that P(CL/GA)‐PEG micelles are promising for prolonged release of hydrophobic drugs.     

New Poly(propylene glycol)‐ and Poly(ethylene glycol)‐Based Polymer Gelators with L‐Lysine

Summary: New polymer gelators consisting of poly(propylene glycol) or poly(ethylene glycol) and L ‐lysine‐based low‐molecular‐weight gelators have been developed. These polymer gelators were synthesized according to a simple procedure with high reaction yield, and formed organogels in many organic solvents. The organogelation mechanism was proposed from the transmission electron microscopy and FTIR spectroscopy studies.

Structures of the polymer gelators synthesized here.     

Synthesis and characterization of poly(ethylene glycol) methyl ether endcapped poly(ethylene terephthalate)

Linear and branched poly(ethylene terephthalate) (PET) copolymers with polyethylene glycol) (PEG) methyl ether (700 or 2000 g/mol) end groups were synthesized using conventional melt polymerization. DSC analysis demonstrated that low levels of PEG end groups accelerated PET crystallization. The incorporated PEG end groups also decreased the crystallization temperature of PET dramatically, and copolymers with a high content of PEG (>17.6 wt%) were able to crystallize at room temperature. Rheological analysis demonstrated that the presence of PEG end groups effectively decreased the melt viscosities and facilitated melt processing. XPS and ATR-FTIR revealed that the PEG end groups tended to aggregate on the surface, and the surface of compression molded films containing 34.0 wt% PEG were PEG rich (85 wt% PEG). PEG end-capped PET (34.0 wt% PEG) and PET films were immersed into a fibrinogen solution (0.7 mg/mL BSA) for 72 h to investigate the propensity for protein adhesion. XPS demonstrated that the concentration of nitrogen (1.05%) on the surface of PEG endcapped PET film was statistically lower than PET (7.67%). SEM analysis was consistent with XPS results, and revealed the presence of adsorbed protein on the surface of PET films.     

Biodegradable electrospun mat: Novel block copolymer of poly (p‐dioxanone‐co‐L‐lactide)‐block‐poly(ethylene glycol)

Ultrafine fibers of a laboratory‐synthesized new biodegradable poly(p‐dioxanone‐co‐L ‐lactide)‐block‐poly(ethylene glycol) copolymer were electrospun from solution and collected as a nonwoven mat. The structure and morphology of the electrospun membrane were investigated by scanning electron microscopy, differential scanning calorimetry (DSC), wide‐angle X‐ray diffraction (WAXD), and a mercury porosimeter. Solutions of the copolymer, ranging in the lactide fraction from 60 to 80 mol % in copolymer composition, were readily electrospun at room temperature from solutions up to 20 wt % in methylene chloride. We demonstrate the ability to control the fiber diameter of the copolymer as a function of solution concentration with dimethylformamide as a cosolvent. DSC and WAXD results showed the relatively poor crystallinity of the electrospun copolymer fiber. Electrospun copolymer membrane was applied for the hydrolytic degradation in phosphate buffer solution (pH = 7.5) at 37 °C. Preliminary results of the hydrolytic degradation demonstrated the degradation rate of the electrospun membrane was slower than that of the corresponding copolymers of cast film. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 1955–1964, 2003     

Biocompatible poly(ethylene glycol)‐poly(γ‐cholesterol‐L‐glutamate) copolymers: Synthesis,characterization, and in vitro studies

A novel amphiphilic poly(ethylene glycol)‐block‐poly(γ‐cholesterol‐L ‐glutamate) (mPEG–PCHLG) diblock copolymer has been synthesized. The mPEG–PCHLG copolymer has good biocompatibility and low toxicity. The mPEG–PCHLG copolymers could aggregate into nanoparticles with PCHLG blocks as the hydrophobic core and PEG blocks as the hydrophilic shell through emulsion solvent evaporation method. The copolymers were characterized by nuclear magnetic resonance spectroscopy, mass spectrum, Fourier transform infrared spectroscopy, and gel permeation chromatography. The particle sizes, size distributions, and zeta potentials of nanoparticles can also be determined by dynamic light scattering and transmission electron microscopy. This work provides a new and facile approach to prepare amphiphilic block copolymer nanoparticles with controllable performances. This novel copolymer may have potential applications in drug delivery and bioimaging applications.© 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis of novel poly(ethylene glycol)‐containing imidazolium‐functionalized phosphine ligands and their application in the hydrosilylation of olefins

A series of polyethylene glycol‐containing imidazolium‐functionalized phosphine ligands (mPEG‐im‐PPh₂) were successfully synthesized and used in the rhodium‐catalyzed hydrosilylation of olefins. The results indicate that the RhCl₃/mPEG‐im‐PPh₂ catalytic system exhibits both excellent activity and selectivity for the β‐adduct. In addition, the catalytic system may be recycled at least six times.     

Fabrication of Poly(L‐lactide)‐block‐Poly(ethylene glycol)‐block‐Poly(L‐lactide) Triblock Copolymer Thin Films with Nanochannels: An AFM Study

This paper aims to report the fabrication of biodegradable thin films with micro‐domains of cylindrical nanochannels through the solvent‐induced microphase separation of poly(L ‐lactide)‐block‐poly(ethylene glycol)‐block‐poly(L ‐lactide) (PLA‐b‐PEG‐b‐PLA) triblock copolymers with different block ratios. In our experimental scope, an increase in each of the block lengths of the PLA and PEG blocks led to both a variation in the average number density (146 to 32 per 100 µm²) and the size of the micro‐domains (140 to 427 nm). Analyses by atomic force microscopy (AFM) and fluorescence microscopy indicated that the hydrophilic PEG nanochannels were dispersed in the PLA matrix of the PLA‐b‐PEG‐b‐PLA films. We demonstrated that the micro‐domain morphology could be controlled not only by the block length of PEG, but also by the solvent evaporation conditions.