Physical, Electrochemical, and Solvent Permeation Properties of Amphiphilic Conetwork Membranes Formed through Interlinking of Poly(vinylidene fluoride)-Graft-Poly[(2-dimethylamino)ethyl Methacrylate] with Telechelic Poly(ethylene glycol) and Small Molecular Weight Cross-Linkers.

We report the preparation of dense and porous amphiphilic conetwork (APCN) membranes through the covalent interconnection of poly(vinylidene fluoride)-graft-poly[(2-dimethylamino)ethyl methacrylate] (PVDF-g-PDMAEMA) copolymers with telechelic poly(ethylene glycol) (PEG) or α,α-dichloro-p-xylene (XDC). The dense APCN membranes exhibit varying solvent swelling and mechanical properties depending on the compositions and overall crystallinity. The crystallinity of both PVDF (20-47%) and PEG (9-17%) is significantly suppressed in the dense APCNs prepared through the interconnection of PVDF-g-PDMAEMA with reactive PEG as compared to the APCN membranes (48-53%) prepared with XDC as well as mechanical blend of PVDF-g-PDMAEMA plus nonreactive PEG. The dense APCN membranes exhibit a good transport number of monovalent ions and ionic conductivity. The APCN membrane interconnected with PEG and containing binary ionic liquids exhibits a room-temperature lithium ion conductivity of 0.52 mS/cm. On the other hand, APCN ultrafiltration (UF) membranes exhibit organic solvent-resistant behavior. The UF membrane obtained by interconnecting PVDF-g-PDMAEMA with telechelic PEG shows low protein fouling propensity, higher hydrophilicity, and water flux as compared to membranes prepared using XDC as the interconnecting agent. The significant effect of the covalent interconnection of the amphiphilic graft copolymers with telechelic PEG or XDC on the overall properties provides a good opportunity to modulate the properties and performance of APCN membranes.

Library of Derivatizable Multiblock Copolymers by Nucleophilic Substitution Polymerization and Targeting Specific Properties.

Multiblock copolymers (MBCs) are fascinating in the field of biology-polymer chemistry interfaces. Synthesizing libraries of MBCs with tailor-made functionality is challenging as it involves multiple steps. Herein, a simple synthesis, analogous to polyurethane/Michael addition reactions, has been introduced to obtain a library of derivatizable MBCs. Nucleophilic substitution polymerization (SNP) of poly(ε-caprolactone) and poly(ethylene glycol) blocks containing activated halide termini by primary mono/di/coamines or clickable amines provides functional MBCs. The structure of amines directs the properties of the MBCs. The self-assembly of small molecular weight primary diamine-based MBCs shows controlled release of hydrophobic model guest molecules and therapeutics. The primary diamine (no dangling chain) helps to form MBC micelles having a relatively tight core with a low diffusion property. Antimicrobial property in the MBCs has been introduced by separating the cationic centers from the lipophilic groups using a coamine as a nucleophilic agent and a small molecular weight dihalide as a chain extender. Clickable MBCs were synthesized by changing the structure of the nucleophile to obtain degradable amphiphilic conetworks and hydrogels. Varieties of macromolecular entities could be obtained by switching the nucleophilic agent and introducing a small molecular weight chain extender. This synthesis approach provides an opportunity to tune the chemical functionality, topological structure, and biological properties of macromolecular entities.

Gold Nanoparticle Promoted Formation and Biological Properties of Injectable Hydrogels.

Acceleration of gelation in the biological environment and improvement of overall biological properties of a hydrogel is of enormous importance. Biopolymer stabilized gold (Au) nanoparticles (NPs) exhibit cytocompatibility and therapeutic activity. Hence, in situ gelation and subsequent improvement in the property of a hydrogel by employing Au NPs is an attractive approach. We report that stable Au NPs accelerate the conventional nucleophilic substitution reaction of activated halide-terminated poly(ethylene glycol) and tertiary amine functional macromolecules, leading to the rapid formation of injectable nanocomposite hydrogels in vivo and ex vivo with improved modulus, cell adhesion, cell proliferation, and cytocompatibility than that of a pristine hydrogel. NP surfaces with low chain grafting density and good colloidal stability are crucial requirements for the use of these NPs in the hydrogel formation. Influence of the structure of the amine functional prepolymer, the spacer connecting the halide leaving groups of the substrate, and the structure of the stabilizer on the rate promoting activity of the NPs have been evaluated with model low-molecular-weight substrates and macromolecules by 1H NMR spectroscopy, rheological experiments, and density functional theory. Results indicate a significant effect of the spacer connecting the halide leaving group with the macromolecule. The Au nanocomposite hydrogels show sustained co-release of methotrexate, an anti-rheumatic drug, and the Au NPs. This work provides insights for designing an injectable nanocomposite hydrogel system with multifunctional property. The strategy of the use of cytocompatible Au NPs as a promoter provides new opportunity to obtain an injectable hydrogel system for biological applications.

Protonation-induced pH increase at the triblock copolymer micelle interface for transient membrane permeability at neutral pH.

Achieving controlled membrane permeability using pH-responsive block copolymers is crucial for selective intercellular uptake. We have shown that the pH at the triblock-copolymer micelle interface as compared to its bulk pH can help regulate membrane permeability. The pH-dependent acid/base equilibriums of two different interface-interacting pH probes were determined in order to measure the interfacial pH for a pH-responsive triblock copolymer (TBP) micelle under a wide range of bulk pH (4.5-9.0). According to 1H NMR studies, both pH probes provided interfacial pH at a similar interfacial depth. We revealed that the protonation of the amine moiety at the micelle interface and the subsequent formation of a positive charge caused the interface to become relatively less acidic than that of the bulk as well as an increase in the bulk-to-interfacial pH deviation (ΔpH) from ∼0.9 to 1.9 with bulk pH reducing from 8.0 to 4.5. From the ΔpH vs. interface and bulk pH plots, the apparent and intrinsic protonations or positive charge formation pKa values for the micelle were estimated to be ∼7.3 and 6.0, respectively. When the TBP micelle interacted with an anionic large unilamellar vesicle (LUV) of a binary lipid (neutral and anionic) system at the bulk pH of 7.0, fluorescence leakage studies revealed that the pH increase at the micelle interface from that of the LUV interface (pH ∼ 5.5) made the micelle interface partially protonated/cationic, thereby exhibiting transient membrane permeability. Although the increasing interface protonation causes the interface to become relatively less acidic than the bulk at any bulk pH below 6.5, the pH increase at the micelle interface may not be sufficiently large to maintain the threshold for the amine-protonated condition for effecting transient leakage and therefore, a continuous leakage was observed due to the slow disruption of the lipid bilayer.

Self-Assembly of Partially Alkylated Dextran- graft-poly[(2-dimethylamino)ethyl methacrylate] Copolymer Facilitating Hydrophobic/Hydrophilic Drug Delivery and Improving Conetwork Hydrogel Properties.

Key issues of injectable hydrogels are incapability of loading hydrophobic drugs due to insolubility of drugs in aqueous prepolymer solution as well as in hydrogel matrix, and high water swelling, which leads to poor mechanical and bioadhesive properties. Herein, we report that self-assembly of partially long-chain alkylated dextran- graft-poly[(2-dimethylamino)ethyl methacrylate] copolymer in aqueous solution could encapsulate pyrene, a hydrophobic probe, griseofulvin, a hydrophobic antifungal drug, and ornidazole, a hydrophilic antibiotic. Addition of activated chloride terminated poly(ethylene glycol) (PEG) into the guest molecules loaded copolymer solution produced an injectable dextran- graft-poly[(2-dimethylamino)ethyl methacrylate]-linked-PEG conetwork hydrogel. The alkylated hydrogels exhibited zero order release kinetics and were mechanically tough (50-54 kPa storage modulus) and bioadhesive (8-9 kPa). The roles of alkyl chains and dextran on the drug loading-release behavior, degradation behavior, gelation time, and the mechanical property of the hydrogels have been studied in details. Additionally, DNA hybrid composite hydrogel was formed owing to the cationic nature of the prepolymer solution and the hydrogel. Controlled alkylation of a prepolymer thus highlights the potential to induce and enhance the hydrogel property.

Synthesis and Multi-Responsive Self-Assembly of Cationic Poly(caprolactone)-Poly(ethylene glycol) Multiblock Copolymers.

Individual dissimilar blocks were combined to obtain well-defined An Bn and (A-B-A)n types of cationic amphiphilic multiblock copolymers (MBCs) through mild sequential nucleophilic substitution without formation of byproducts. MBCs were synthesized by reacting end-functional polymer blocks of poly(caprolactone) (PCL), poly(ethylene glycol) (PEG), and PCL-b-PEG-b-PCL. For selective degradation, acid- and base-labile ester as well as reducible disulfide groups were introduced as linkers between the blocks. The micellar self-assemblies of these MBCs showed exceptional stability under normal physiological conditions with negligible release of the guest molecules. Selective disassembly under mildly acidic and basic conditions or in the presence of reducing agents caused triggered release of the guest molecules. This strategy is versatile and opens an opportunity to obtain a variety of tailor-made MBCs for selective and triggered release of therapeutics.

A simple interfacial pH detection method for cationic amphiphilic self-assemblies utilizing a Schiff-base molecule.

A simple pH-sensing method for cationic micelle and vesicle interfaces is introduced, utilizing a Schiff-base molecule, 2-((4H-1,2,4-triazol-4-ylimino)methyl)-6-(hydroxymethyl)-4-methylphenol (AH). AH containing a phenolic moiety was obtained by the reaction between 4-amino-4H-1,2,4-triazole containing polar O- and N-centres with opposite polarity to the cationic interface and 2-hydroxy-3-(hydroxymethyl)-5-methylbenzaldehyde. The acid/base equilibrium of AH was investigated at the interfaces of cetrimonium bromide (CTAB) micelles, tri-block-copolymeric micelles (TBPs) and large unilamellar vesicles (LUVs) of different lipid compositions using steady state UV-Vis absorption spectroscopy. AH interacted strongly with the micelle and vesicle interfaces, according to the binding studies with LUV. A larger amount of AH proton dissociation was observed when localized at the interface of micelles and vesicles compared to that in the bulk phase, indicating that the pH values at the cationic interfaces are higher than in the bulk phase. The pH values were about 2.2 and 1.6 units higher at the CTAB and TBP micelle interfaces, respectively, than the bulk pH. The pH variation decreased from 2.4 to 1.5 units by increasing the neutral 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) lipid content from 0 to 50% in the cationic dimethyldioctadecylammonium (DDAB) LUV, indicating that the interfacial positive charges are responsible for the higher interfacial pH. Detailed structural and absorption characteristics of neutral AH and its anionic A(-) forms were investigated by fluorescence spectroscopic measurements and DFT based theoretical calculations. The present simple pH detection method may be applied to various biological micelle and vesicle interfaces.

A ratiometric solvent polarity sensing Schiff base molecule for estimating the interfacial polarity of versatile amphiphilic self-assemblies.

A newly synthesised Schiff base molecule (PMP) existing in equilibrium between non-ionic and zwitterionic forms displays solvent polarity induced ratiometric interconversion from one form to another, such novelty being useful to detect the medium polarity. The specific interface localisation of PMP in versatile amphiphilic self-assembled systems has been exploited to monitor their interfacial polarity by evaluating such interconversion equilibrium with simple UV-Vis spectroscopy. In spite of the large differences in pH and/or viscosity between the bulk and interface, the unchanged equilibrium between the two molecular forms on varying the medium pH or viscosity provides a huge advantage for the exclusive detection of interfacial polarity.

Low Fouling Polyelectrolyte Layer-by-Layer Self-Assembled Membrane for High Performance Dye/Salt Fractionation: Sequence Effect of Self-Assembly.

Layer-by-layer (LbL) self-assembly of oppositely charged polyelectrolytes (PEs) is usually performed on a conventional ultrafiltration base substrate (negative zeta potential) by depositing a cationic PE as a first layer. Herein, we report the facile and fast formation of high performance molecular selective membrane by the nonelectrostatic adsorption of anionic PE on the polyvinylidene fluoride (PVDF, zeta potential -17 mV) substrate followed by the electrostatic LbL assembly. Loose nanofiltration membranes have been prepared via both concentration-polarization (CP-LbL, under applied pressure) driven and conventional (C-LbL, dipping) LbL self-assembly. When the first layer is poly(styrene sodium) sulfonic acid, the LbL assembled membrane contains free -SO3- groups and exhibits higher rejection of Na2SO4 and lower rejection of MgCl2. The reversal of salt rejection occurs when the first layer is quaternized polyvinyl imidazole (PVIm-Me). The membrane (five layers) prepared by first depositing PStSO3Na shows higher rejection of several dyes (97.9 to >99.9%), higher NaCl to dye separation factor (52-1800), and higher dye antifouling performance as compared to the membrane prepared by first depositing PVIm-Me (97.5-99.5% dye rejection, separation factor ∼40-200). However, the C-LbL membrane requires a longer time of self-assembly or higher PE concentration to reach a performance close to the CP-LbL membranes. The membranes exhibit excellent pressure, pH (3-12), and salt (60 g L-1) stability. This work provides an insight for the construction of low fouling and high-performance membranes for the fractionation of dye and salt based on the LbL self-assembly sequence.

Structurally Heterogeneous Amphiphilic Conetworks of Poly(vinyl imidazole) Derivatives with Potent Antimicrobial Properties and Cytocompatibility.

We report the construction of amphiphilic conetwork (APCN)-based surfaces with potent antimicrobial activity and biofilm inhibition ability. The construction strategy is based on the separation of lipophilic alkyl groups (>C6) from the cationic network to obtain good antibacterial properties. The reaction of partially alkylated poly(vinyl imidazole) with the activated halide compounds followed by coating a glass or poly(dimethylsiloxane) (PDMS) sheet leads to the formation of the APCN surface. The dangling alkyl chains, crosslinking junctions, and unreacted vinyl imidazole groups are heterogeneously distributed in the APCNs. The swelling, mechanical property, and phase morphology of the APCN films have been evaluated. Bacterial cell disrupting potency of the APCN coatings increases with increasing alkyl chain length from C6 to C18 with somewhat more of an effect on Escherichia coli as compared to Bacillus subtilis bacteria. The minimum inhibitory amount of the APCNs on glass and a hydrophobic PDMS surface is in the range of 0.02-0.04 mg/cm2 depending on the chain length of the alkyl and the degree of quaternization. The effect of the type of crosslinker for the construction of the conetwork on the antimicrobial property has been evaluated to elucidate the exclusive design of the APCNs. The APCN-based coatings provide potent biocidal activity without much negatively affecting the hemocompatibility and cytocompatibility. These APCNs provide a good model system for comparative evaluation of the biocidal property and structural effect on the biocidal activity.

Poly(vinylidene fluoride)/partially alkylated poly(vinyl imidazole) interpolymer ultrafiltration membranes with intrinsic anti-biofouling and antifouling property for the removal of bacteria.

Bacterial contaminated water causes potential health issues. Conventional chlorine treatment has shortcomings of environmental hazards and chlorine adoptability by the bacterial cells. Ultrafiltration membrane can intercept bacterial species from feed water. Membrane having anti-biofouling/antifouling properties is needed for the removal of bacteria from feed water. Herein, interpolymer membranes with inherent antimicrobial activity and fouling release property have been prepared by the blend of poly(vinylidene fluoride) (PVDF), poly(vinyl pyrrolidone) and partially long chain alkylated (C12 chain) poly(vinyl imidazole) copolymer (PVIm-co-PVIm-C12) followed by cross-linking of the remaining VIm groups with an activated di-halide compound. The membranes obtain with copolymers of degree of alkyl substitution (DSC12) in the range of 0.75-0.85 and amount in the range of 0.9-3.5% w/w in the casting solutions exhibit good antimicrobial activity (>99 % of inhibition) and dynamic anti-biofouling property. The membrane prepared with 0.9% w/w of the copolymer (DSC12=0.85) shows higher flux recovery ratio (91 % for bacterial filtration and 88 % for protein filtration) compare to a pristine membrane (57 % for bacterial filtration and 58 % for protein filtration). The membrane is able to reject the bacteria completely. Use of small amount of copolymer and facile fabrication of stable anti-biofouling/antifouling membranes show potential for the purification of bacterial contaminated water.

Modulation of Properties through Covalent Bond Induced Formation of Strong Ion Pairing between Polyelectrolytes in Injectable Conetwork Hydrogels.

In situ simultaneous formation of both covalent linkages and ion pair is challenging yet necessary to control the biological properties of a hydrogel. We report that the generation of covalent linkages (+N-C) facilitates the simultaneous formation of ion pairs between polyelectrolytes (PEs) in a hydrogel network. Co-injection of tertiary amine functional macromolecules and reactive poly(ethylene glycol) (PEG) containing negatively charged PE leads to the formation of hydrogel conetworks consisting of covalent junctions and ion pairs. Our design is based on the gradual appearance of +N-C junctions followed by formation of ion pairs. This strategy provides an easy access to hydrogel networks bearing a predetermined proportion of ion pair and covalent cross-linking junction. The proportion of ion pair could be varied by introducing a precalculated proportion of mono- and difunctional reactive PEG in the hydrogel system. The topology of the prepolymer and the hydrogel could be modulated (graft) during hydrogel formation. This approach is applicable to obtain covalent/ionic, covalent bond induced purely ionic, and purely covalent hydrogels of several macromolecular entities. The effect of ion pairing in the hydrogels is strongly reflected in the modulus, strain bearing, degradation, free volume, swelling, and drug release properties. The hydrogels exhibit microscopic recovery of modulus after application of high amplitude strain depending on the prepolymer concentration (chain entanglement) and nature of hydrogel network. The hydrogels are hemocompatible, and the covalent/ionic hydrogels show a slower release of methotrexate than that of the purely covalent hydrogel. This work provides an understanding for the in situ construction and manipulation of biological properties of hydrogels through the covalent bond induced formation of a strong ion pair.

PEGylated gold nanoparticles promoted rapid macromolecular chain-end transformation and formation of injectable hydrogels.

Azide-alkyne click cycloaddition and Michael addition reactions are useful for the synthesis and modification of biologically relevant macromolecules. Acceleration of these reactions at the macromolecular chain-ends and backbone has been achieved by gold [Au-(PEG-SH)n] nanoparticles (NPs) stabilized with multi-thiol-functional poly(ethylene glycol) containing tertiary amine groups in its backbone. The Au NPs successfully activate electron rich alkyne and acrylate functionalities of macromolecules at low substrate concentration leading to the enhancement of the reaction rate. The Au NPs successfully accelerate the gelation rate of reactive prepolymers leading to the rapid formation of injectable hydrogels. The Au nanocomposite hydrogels exhibited higher ultimate modulus and porosity than those of the pristine hydrogels. The grafting density (chains per nm2) of the stabilizer onto the Au NP surface plays a crucial role towards the activity of the NPs. The conversion of the chain-end functionality and gelation rate increase with decreasing grafting density onto the NP surface. A high grafting density lowers the activity of the Au NPs through blocking the active metal surface. The developed Au NPs may be a potential agent for the rapid preparation of biologically relevant macromolecular entities.

Correction: Sustainable process for the preparation of potassium sulfate by electrodialysis and its concentration and purification by a nanofiltration process.

[This corrects the article DOI: 10.1039/C6RA14303B.].

Liquid Prepolymer-Based in Situ Formation of Degradable Poly(ethylene glycol)-Linked-Poly(caprolactone)-Linked-Poly(2-dimethylaminoethyl)methacrylate Amphiphilic Conetwork Gels Showing Polarity Driven Gelation and Bioadhesion.

Amphiphilic conetwork (APCN) gels suffer from lack of direct injectability due to use of organic solvent, prolonged crosslinking/polymerization process and immiscibility between hydrophilic and hydrophobic prepolymers. On the basis of prepolymers compatibility and polarity, we report the use of an advanced prepolymer liquid system for in situ construction of APCN gels. Solid elastic poly(ethylene glycol)-linked-poly(ε-caprolactone)-linked-poly(2-dimethylaminoethyl)methacrylate (PEG-l-PCL-l-PDMA) APCN gels were formed upon addition of an appropriate amount of PDMA diluted in nonreactive sacrificial liquid PEG into a compatible blend of activated halide terminated PEG and PCL liquids. Compatibility among the prepolymers allowed favorable gelation. The polarity of the prepolymer liquid greatly influenced the gelation time. PEG-l-PCL-l-PDMA APCN gels were cytocompatible/biodegradable and showed storage modulus in the range of 50-200 kPa and bioadhesive strength of 40-90 kPa. The fluorescence experiments showed that the hydrophobic probe, pyrene was distributed in both hydrophilic and hydrophobic phases of the APCN gels. These APCNs exhibited sustained release of hydrophobic and hydrophilic drugs. Effects of polarity, composition, and molecular weight of the liquid prepolymers on the gelation time, rheological property, and swelling behavior of the APCN gels have been investigated in details.

Anti-organic fouling and anti-biofouling poly(piperazineamide) thin film nanocomposite membranes for low pressure removal of heavy metal ions.

Propensity towards anti-organic fouling, anti-biofouling property and low rejection of multivalent cation (monovalent counter ion) restricts the application of the state-of-art poly(piperazineamide) [poly(PIP)] thin film composite (TFC) nanofiltration (NF) membrane for the treatment of water containing toxic heavy metal ions, organic fouling agents and microbes. Herein, we report the preparation of thin film nanocomposite (TFNC) NF membranes with improved heavy metal ions rejection efficacy, anti-biofouling property, and anti-organic fouling properties compared to that of poly(PIP) TFC NF membrane. The TFNC NF membranes were prepared by the interfacial polymerization (IP) between PIP and trimesoyl chloride followed by post-treatment with polyethyleneimine (PEI) or PEI-polyethylene glycol conjugate and then immobilization of Ag NP. The IP was conducted on a polyethersulfone/poly(methyl methacrylate)-co-poly(vinyl pyrollidone)/silver nanoparticle (Ag NP) blend ultrafiltration membrane support. The TFNC membranes exhibited >99% rejection of Pb2+, 91-97% rejection of Cd2+, 90-96% rejection of Co2+ and 95-99% rejection of Cu2+ with permeate flux ∼40Lm-2h-1 at applied pressure 0.5MPa. The improved heavy metal ions rejection efficacy of the modified NF membranes is attributed to the development of positive surface charge as well as lowering of surface pore size compared to that of unmodified poly(PIP) TFC NF membrane.

Synthesis of block copolymer-stabilized Au-Ag alloy nanoparticles and fabrication of poly(methyl methacrylate)/Au-Ag nanocomposite film.

[Poly(2-(N,N-dimethylamino)ethyl methacrylate)]-b-poly(methyl methacrylate)-b-[poly(2-(N,N-dimethylamino)ethyl methacrylate)] (M(n)=45,000; 20K-5K-20K; PDI = 1.2) block copolymer surfactant stabilized amphiphilic gold-silver alloy nanoparticles (Au-Ag(PDMA-b-PMMA-b-PDMA)) has been synthesized in both water and in organic medium. The block copolymer stabilized pre-made alloy nanoparticles were successfully dispersed in hydrophobic poly(methyl methacrylate) homopolymer matrix (PMMA) of molecular weight 30,000. The successful synthesis of alloy nanoparticles was accessed by Transmission Electron Microscope (TEM), Energy Dispersed X-ray (EDX), and UV-visible spectrophotometric analysis. The surface functionality of the nanoparticles was confirmed by quantitative determining the grafting density of polymer chain around the nanoparticle surface using combination of thermo gravimetric (TGA) and TEM analysis. The hydrodynamic diameter of the alloy particles including the polymer chains was obtained from dynamic light scattering measurement (DLS). The mechanism of synthesis of high concentration of Au-Ag alloy particles from HAuCl(4) and AgNO(3) (in presence of Cl(-) from reduction of gold salt) metal particles precursors and the successful preparation of poly(methyl methacrylate)/gold-silver nanocomposite films have been discussed.

Dually crosslinked injectable hydrogels of poly(ethylene glycol) and poly[(2-dimethylamino)ethyl methacrylate]-b-poly(N-isopropyl acrylamide) as a wound healing promoter.

Rapid gelation, low heat generation, biocompatibility, biodegradability, avoiding the use of a small molecular weight gelator and high gel fraction are the essential criteria for the successful biomedical application of an injectable hydrogel. We have developed a series of dually crosslinked injectable hydrogels of PEG and poly[2-(dimethylamino)ethyl methacrylate]-b-poly(N-isopropyl acrylamide) through extremely simple chemistry. The sequential nucleophilic substitution reaction between PEG containing reactive termini and the copolymer provided chemically crosslinked hydrogels with a gel fraction as high as 96-99% with a gelation time of 1-4 min under physiological conditions. The gelation occurred with ca. 1 °C rise in temperature per gram of the injectable solution, avoids formation of by-products and can be performed in the temperature range of 20-37 °C. The hydrogels undergo hardening at a physiological temperature as confirmed by rheological experiments. The gelation time, water swelling, mechanical properties and degradability of the hydrogels depend on the PEG to copolymer ratio in the injectable solution. The rheological behaviour of the fully hydrated hydrogels showed desirable mechanical properties for soft tissue regeneration. The hydrogels exhibited blood compatibility and retained the viability of HepG2 cells with time. Platelet adhesion and aggregation followed by fibrinogen adsorption ability makes these hydrogels suitable for wound healing applications.

Multifunctionalization of Poly(vinylidene fluoride)/Reactive Copolymer Blend Membranes for Broad Spectrum Applications.

Simultaneous immobilization and cross-linking of antifouling/low toxic polymers, e.g., poly(ethylenimine) (PEI), dextran (Dex), agarose (Agr), poly(ethylene glycol) (PEG), PEI-Dex, and PEI-PEG conjugates, and stimuli-responsive copolymers on a porous membrane surface in mild reaction conditions is desirable for the enhancement of hydrophilicity, antifouling character, cytocompatibility, and inducing stimuli-responsive behavior. Grafting to technique is required since the precursors of most of these macromolecules are not amenable to surface-initiated polymerization. In this work, we report a versatile process for the simultaneous immobilization and cross-linking of a library of macromolecules on and into the blend membrane (PVDF-blend) of poly(vinylidene fluoride) and poly(methyl methacrylate)-co-poly(chloromethylstyrene). Sequential nucleophilic substitution reaction between activated halide moieties of the copolymer and amine groups of different macromolecules readily provided series of modified membranes. These membranes exhibited antifouling property superior to that of the unmodified membrane. The effectiveness of this technique has been demonstrated by the immobilization of pH or both pH- and temperature-responsive copolymer on PVDF-blend membrane for responsive separation of poly(ethylene oxide) and bovine serum albumin. Silver nanoparticles were also anchored on the select modified membranes surfaces for the enhancement of antibiofouling property. Our approach is useful to obtain verities of functional membranes and selection of membrane for a particular application.

Effect of Polyethylene Glycol on Properties and Drug Encapsulation-Release Performance of Biodegradable/Cytocompatible Agarose-Polyethylene Glycol-Polycaprolactone Amphiphilic Co-Network Gels.

We synthesized agarose-polycaprolactone (Agr-PCL) bicomponent and Agr-polyethylene glycol-PCL (Agr-PEG-PCL) tricomponent amphiphilic co-network (APCN) gels by the sequential nucleophilic substitution reaction between amine-functionalized Agr and activated halide terminated PCL or PCL-b-PEG-b-PCL copolymer for the sustained and localized delivery of hydrophilic and hydrophobic drugs. The biodegradability of the APCNs was confirmed using lipase and by hydrolytic degradation. These APCN gels displayed good cytocompatibility and blood compatibility. Importantly, these APCN gels exhibited remarkably high drug loading capacity coupled with sustained and triggered release of both hydrophilic and hydrophobic drugs. PEG in the APCNs lowered the degree of phase separation and enhanced the mechanical property of the APCN gels. The drug loading capacity and the release kinetics were also strongly influenced by the presence of PEG, the nature of release medium, and the nature of the drug. Particularly, PEG in the APCN gels significantly enhanced the 5-fluorouracil loading capacity and lowered its release rate and burst release. Release kinetics of highly water-soluble gemcitabine hydrochloride and hydrophobic prednisolone acetate depended on the extent of water swelling of the APCN gels. Cytocompatibility/blood compatibility and pH and enzyme-triggered degradation together with sustained release of drugs show great promise for the use of these APCN gels in localized drug delivery and tissue engineering applications.