PNIPAM Chains Research Articles

Thermoresponsive behavior of poly(N-isopropylacrylamide)s with dodecyl and carboxyl terminal groups in aqueous solution: pH-dependent cloud point temperature

It was recently reported that poly(N-isopropyl acrylamide) (PNIPAm) polymers synthesized by RAFT polymerization using S-1-dodecyl-S′-(α,α′-dimethyl-α′′-acetic acid)trithiocarbonate as a chain transfer agent form micelles in aqueous solutions with the core of hydrophobic terminal dodecyl groups and the corona of PNIPAm chains with carboxylic groups at the periphery, the ionization of which prevents the micelles from phase separation above the lower critical solution temperature of PNIPAm in water (Langmuir 30:7986–7992). In this paper, we study the pH- and ionic strength-dependence of the aggregation behavior of two HOOC-PNIPAm-C12 polymers, differing in the degree of polymerization, in aqueous solutions. We show that the cloud point temperature (CPT) of HOOC-PNIPAm-C12 can be shifted up to several tens of K by changing pH of the solution. The aggregation of the PNIPAms above the CPT can be efficiently accelerated by screening electrostatic repulsion between PNIPAm micelles by changing ionic strength of the solution.

Hydration-Shell Transformation of Thermosensitive Aqueous Polymers.

Although water plays a key role in the coil-globule transition of polymers and biomolecules, it is not clear whether a change in water structure drives or follows polymer collapse. Here, we address this question by using Raman multivariate curve resolution (Raman-MCR) spectroscopy to investigate the hydration shell structure around poly(N-isopropylacrylamide) (PNIPAM) and poly(propylene oxide) (PPO), both below and above the cloud point temperature at which the polymers collapse and form mesoscopic polymer-rich aggregates. We find that, upon clouding, the water surrounding long PNIPAM chains transforms to a less ordered and more weakly hydrogen bonded structure, while the water surrounding short PNIPAM and PPO chains remains similar above and below the cloud point. Furthermore, microfluidic temperature jump studies demonstrate that the onset of clouding precedes the hydration-shell structural transformation, and thus the observed water structural transformation is associated with ripening of aggregates composed of long-chain polymers, on a time scale that is long compared to the onset of clouding.

Stimuli-Responsive DNA-Based Hydrogels: From Basic Principles to Applications.

The base sequence of nucleic acids encodes structural and functional information into the DNA biopolymer. External stimuli such as metal ions, pH, light, or added nucleic acid fuel strands provide triggers to reversibly switch nucleic acid structures such as metal-ion-bridged duplexes, i-motifs, triplex nucleic acids, G-quadruplexes, or programmed double-stranded hybrids of oligonucleotides (DNA). The signal-triggered oligonucleotide structures have been broadly applied to develop switchable DNA nanostructures and DNA machines, and these stimuli-responsive assemblies provide functional scaffolds for the rapidly developing area of DNA nanotechnology. Stimuli-responsive hydrogels undergoing signal-triggered hydrogel-to-solution transitions or signal-controlled stiffness changes attract substantial interest as functional matrices for controlled drug delivery, materials exhibiting switchable mechanical properties, acting as valves or actuators, and "smart" materials for sensing and information processing. The integration of stimuli-responsive oligonucleotides with hydrogel-forming polymers provides versatile means to exploit the functional information encoded in the nucleic acid sequences to yield stimuli-responsive hydrogels exhibiting switchable physical, structural, and chemical properties. Stimuli-responsive DNA-based nucleic acid structures are integrated in acrylamide polymer chains and reversible, switchable hydrogel-to-solution transitions of the systems are demonstrated by applying external triggers, such as metal ions, pH-responsive strands, G-quadruplex, and appropriate counter triggers that bridge and dissociate the polymer chains. By combining stimuli-responsive nucleic acid bridges with thermosensitive poly(N-isopropylacrylamide) (pNIPAM) chains, systems undergoing reversible solution ↔ hydrogel ↔ solid transitions are demonstrated. Specifically, by bridging acrylamide polymer chains by two nucleic acid functionalities, where one type of bridging unit provides a stimuli-responsive element and the second unit acts as internal "bridging memory", shape-memory hydrogels undergoing reversible and switchable transitions between shaped hydrogels and shapeless quasi-liquid states are demonstrated. By using stimuli-responsive hydrogel cross-linking units that can assemble the bridging units by two different input signals, the orthogonally-triggered functions of the shape-memory were shown. Furthermore, a versatile approach to assemble stimuli-responsive DNA-based acrylamide hydrogel films on surfaces is presented. The method involves the activation of the hybridization chain-reaction (HCR) by a surface-confined promoter strand, in the presence of acrylamide chains modified with two DNA hairpin structures and appropriate stimuli-responsive tethers. The resulting hydrogel-modified surfaces revealed switchable stiffness properties and signal-triggered catalytic functions. By applying the method to assemble the hydrogel microparticles, substrate-loaded, stimuli-responsive microcapsules are prepared. The signal-triggered DNA-based hydrogel microcapsules are applied as drug carriers for controlled release. The different potential applications and future perspectives of stimuli responsive hydrogels are discussed. Specifically, the use of these smart materials and assemblies as carriers for controlled drug release and as shape-memory matrices for information storage and inscription and the use of surface-confined stimuli-responsive hydrogels, exhibiting switchable stiffness properties, for catalysis and controlled growth of cells are discussed.

Effects of stereochemistry and copolymerization on the LCST of PNIPAm.

Poly(N-isopropylacrylamide) (PNIPAm) is a smart polymer that presents a lower critical transition temperature (LCST) of 305 K. Interestingly, this transition point falls within the range of the human body temperature, making PNIPAm a highly suitable candidate for bio-medical applications. However, it is sometimes desirable to have a rather flexible tuning of the LCST of these polymers to further increase their range of applications. In this work, we use all-atom molecular dynamics simulations to study the LCST of PNIPAm-based (co-)polymers. We study different molecular architectures where the polymer sequences are tuned either by modifying its stereochemistry or by the co-polymerization of PNIPAm with acrylamide (Am) units. Our analysis connects global polymer conformations with the microscopic intermolecular interactions. These findings suggest that the collapse of a PNIPAm chain upon heating is dependent on the hydration structure around the monomers, which is strongly dependent on the tacticity and the presence of more hydrophilic acrylamide monomers. Our results are found to be in good agreement with the existing experimental data.

Nanoscale Proteinosomes Fabricated by Self-Assembly of a Supramolecular Protein-Polymer Conjugate.

Proteinosomes are a type of protein-based spherical capsules, which have potential applications in drug delivery, cell imaging, gene expression, and biocatalysis. In this research, a novel approach to the fabrication of proteinosomes entirely composed of protein molecules based on self-assembly of a supramolecular protein-polymer conjugate is proposed. A supramolecular protein-polymer conjugate was prepared by mixing βCD-modified bovine serum albumin (BSA) and adamantane-terminated poly(N-isopropylamide) (Ad-PNIPAM) in aqueous solution. The BSA-PNIPAM bioconjugate self-assembled into micelles with PNIPAM cores and BSA coronae at a temperature above the lower critical solution temperature (LCST) of PNIPAM. After cross-linking of BSA in the coronae, and followed by addition of excess βCD, PNIPAM chains were cleaved from the micellar structures, and nanoscale proteinosomes were prepared. The dual-responsive proteinosomes dissociated in the presence of trypsin or glutathione.

Role of Protecting Groups in Synthesis and Self-Assembly of Glycopolymers.

Protection and deprotection are basic procedures in oligosaccharide synthesis. By taking advantage of the processes of attaching and removing the protecting groups, preparation of oligosaccharides with complex structures can be achieved with relatively high yields. However, the role of protecting groups in solution properties and self-assembly of synthetic glycopolymers has been overlooked in the literature. In this paper, we focused on such effects for well-designed copolymers in which different numbers of benzyl (Bn) groups are installed regioselectively in saccharide rings. Thus, three block copolymers P1, P2, and P3 composed of a common block of PNIPAm and a glycopolymer block with trisaccharide triMan side chains differing in the respective number of Bn (0, 2, and 6) were prepared. The solutions of these block copolymers in water were investigated by dynamic and static light scatting and VT-1H NMR. We found that all of the three copolymers P1, P2, and P3 formed association at room temperature. Particularly, P1 associated loosely due to carbohydrate-carbohydrate interaction (CCI) while P3 formed tight aggregates due to hydrophobic interactions between Bn, and P2 behaved between those of P1 and P3. Moreover, upon heating, phase transition of PNIPAm block took place leading to micelle formation. Hydrodynamic radius of P1 and P2 increased significantly as expected, while P3 did not follow this trend, because during heating, collapse and accumulation of the PNIPAm chains would occur within the tight aggregates mainly, so it leads to a little change of the size.

Bulky 4,6-disubstituted tetraphenylethene-naphthalimide dyad: synthesis, copolymerization, stimuli-responsive fluorescence and cellular imaging.

We report the design and synthesis of a tetraphenylethene substituted with naphthalimide at the 4, 6 positions, named NI-2TPE. NI-2TPE exhibits strong solvent-dependent emission properties with combined ICT and AIE characteristics in THF-H2O systems. This probe was used directly on test papers to distinguish normal organic solvents using their emission colours under UV light based on its AIE and ICT nature. Thanks to the vinyl group in NI-2TPE, we synthesized a copolymer of NIPAM and NI-2TPE, termed P(NIPAM-co-NI-2TPE). The resulting polymer is highly soluble and fluorescent in water (ΦF = 15.4%). Due to the well-known thermo-responsive character of NIPAM, P(NIPAM-co-NI-2TPE) exhibits an interesting fluorescence change in response to various temperatures. Due to the thermo-induced shrinking of the PNIPAM chain, the fluorescence intensity gradually increased from 20 to 34 °C. As the temperature further increased from 34 to 90 °C, the fluorescence intensity decreased sharply, which was caused by the well-known thermal effects. Furthermore, we synthesized a P(HEA-co-NI-2TPE-TPP acrylate) copolymer, in which HEA is a hydrophilic unit, TPP is a mitochondria label and NI-2TPE a fluorescent probe. The corresponding polymer probe is highly soluble in water with FLQY = 7% and we have further applied this probe as a mitochondria targeted imaging tracker in HeLa cells successfully.

Selective solute adsorption and partitioning around single PNIPAM chains.

Thermoresponsive polymer architectures have become integral building blocks of 'smart' functional materials in modern applications. For a large range of developments, e.g. for drug delivery or nanocatalytic carrier systems, the selective adsorption and partitioning of molecules (ligands or reactants) inside the polymeric matrix are key processes that have to be controlled and tuned for the desired material function. In order to gain insights into the nanoscale structure and binding details in such systems, we here employ molecular dynamics simulations of the popular poly(N-isopropylacrylamide) (PNIPAM) polymer in explicit water in the presence of various representative solute types with a focus on aromatic model reactants. We study a single polymer chain and explore the influence of its elongation, stereochemistry, and temperature on the solute binding affinities. While we find that the excess adsorption generally increases with the size of the solute, the temperature-dependent affinity to the chain is highly solute specific and has a considerable dependence on the polymer elongation (i.e. polymer swelling state). We elucidate the molecular mechanisms of the selective binding in detail and eventually present how the results can be extrapolated to macroscopic partitioning of the solutes in swollen polymer architectures, such as hydrogels.

Collapse-Swelling Transitions of a Thermoresponsive, Single Poly(N-isopropylacrylamide) Chain in Water.

We present molecular dynamics (MD) simulations of a single poly(N-isopropylacrylamide) (PNIPAM) chain in explicit water at temperatures between 270 and 320 K near the lower critical solution temperature (LCST). The force-fields of OPLS-AA and TIP4P/2005 are used for a PNIPAM chain and water molecules, respectively. Three independent simulations with durations of 1 μs are performed at each temperature for a 30-mer PNIPAM chain starting with three distinct conformations: extended, loosely collapsed, and tightly collapsed states. The simulation trajectories exhibit reversible conformational transitions between swollen- and collapsed-chain conformations, which has rarely been reported in previous simulation studies, with the overall transition occurring at different temperatures depending on the initial conformation. The inconsistency of the transition temperatures depending on the initial conformation implies that, in spite of the simulation duration of 1 μs distinctly longer than that in previous simulation studies, the conformational sampling from the MD simulations is not enough to draw conclusions on equilibrium properties. Instead of evaluating average properties, therefore, the focus is on dynamic changes in the chain conformation during reversible collapse-swelling transitions at each temperature. The simulation trajectories are analyzed in terms of the radius of gyration, intrachain distances, hydrophobic contacts, and chain-water and intrachain hydrogen bonding. In particular, the formation of stable intrachain hydrogen bonds is a signature of the tightly collapsed-chain conformations that persist, once formed, for the entire simulation duration.

Controlling the aqueous solubility of PNIPAM with hydrophobic molecular units

The effect of co-polymerization of thermo-sensitive polymers with hydrophilic or hydrophobic co-monomers on the LCST and the structure of proximal water remains a fundamental and challenging problem. Here, we employ all-atom molecular dynamics simulations to investigate the aqueous solubility of a thermo-sensitive polymer, poly(N-isopropylacrylamide) (PNIPAM), a hydrophobic polymer polystyrene (PS) and block co-polymers of PNIPAM-co-PS. The simulations of pure oligomers of PNIPAM and PS and their co-polymers are conducted below and above the LCST of PNIPAM to elucidate the effect of increase in number of PS units in PNIPAM-co-PS co-polymers on the coil-to-globule transition of PNIPAM and structure of proximal water. Our simulations suggest that while the LCST of pure PNIPAM oligomers is strongly associated with the structural changes in the proximal water molecules present near PNIPAM, inclusion of PS units disrupts the interactions between PNIPAM and water and promotes the faster dehydration of PNIPAM chains above its LCST. This phenomenon is manifested by a coil-to-globule transition in PNIPAM chains present in PNIPAM-co-PS co-polymers at much shorter times as compared to the pure PNIPAM oligomers. Our results also reveal that with increase in the number of PS units in PNIPAM-co-PS co-polymers the coil-to-globule transition is accelerated.

Rheological properties of suspensions of thermo-responsive poly(N-isopropylacrylamide) microgels undergoing volume phase transition

The rheological properties of suspensions of thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) microgels are investigated in the swollen and collapsed states using oscillatory and long-time creep measurements. In the swollen state with repulsive interparticle interaction, the zero shear viscosity and quasi-plateau modulus are solely governed by the effective volume fraction (φeff) and are independent of temperature, particle diameter and particle concentration. The long-time creep tests reveal that in the collapsed state with attractive interparticle interactions, the moderately concentrated suspensions with φeff≈0.5 become viscoelastic liquids with high viscosities of >105 Pas and long-terminal relaxation times of >103 s due to the formation of a network-like aggregation of particles, whereas the suspensions with the same φeff in the swollen state exhibit a Newtonian flow with low viscosities of less than 10−1 Pas. The network-like aggregation of particles is so fragile that it can be broken by a very small stress of several Pascals. The modulus and viscosity in the collapsed state depend on both φeff and temperature: the modulus and viscosity increase, as the temperature increases due to an increase in the hydrophobic nature of the PNIPAM chains, which govern the attractive interparticle interaction. The particle aggregations in the collapsed state considerably lower the threshold value of φeff (φc), above which the infinite percolation clusters are formed, as compared with the values of φc in the swollen state and for the random close packing of hard spheres. The rheological properties of the suspensions of thermo-responsive poly(N-isopropylacrylamide) microgels are investigated in the swollen and collapsed states using creep and oscillatory measurements. The results from the long-time creep tests reveal that in the collapsed state with attractive interparticle interactions, the suspensions with a particle volume fraction of approximately 0.5 become viscoelastic liquids with high viscosities due to the formation of a network-like aggregation of particles. However, the suspensions with the same volume fraction in the swollen state exhibit a Newtonian fluid behavior with low viscosities.

Refined control of thermoresponsive swelling/deswelling and drug release properties of poly(N-isopropylacrylamide) hydrogels using hydrophilic polymer crosslinkers

Thermoresponsive poly(N-isopropylacrylamide) (PNIPAm)-based hydrogels are widely investigated for their ability to alter their physical properties (e.g. dimensions, swelling/deswelling) in response to change in temperature. Despite extensive research efforts, it is still challenging to control various aspects of thermoresponsive physical properties of PNIPAm hydrogels in an efficient and comprehensive manner using conventional small molecular crosslinkers due to their limited solubility and functional groups. Herein, thermoresponsive swelling/deswelling behavior of PNIPAm hydrogels is tuned in a wide range by hydrophilic polymeric crosslinkers with varying chain lengths. The concentration and molecular weight of the poly(ethylene glycol) (PEG) crosslinker are varied to control the swelling/deswelling behavior, drug release, and lower critical solution temperature (LCST) of PNIPAm-PEG hydrogels. Compared with PNIPAm hydrogels crosslinked with a conventional small molecular crosslinker, N,N′-methylenebisacrylamide, greater degree and range of thermoresponsive swelling/deswelling as well as tunable LCST are demonstrated for PNIPAm-PEG hydrogels. In addition, more swelling-controlled PNIPAm-PEG hydrogels displayed more sustained and variable thermoresponsive drug release based on their crosslinking density, by modulating the hydrophobic transition of PNIPAm chains with hydrophilic PEG chains. In sum, various thermoresponsive properties of PNIPAm hydrogels could be controlled by hydrophilic polymeric crosslinkers, and this strategy could be applied to various hydrogel systems to control their physical properties for biomedical applications.

Solvent Dynamics in Solutions of PNIPAM in Water/Methanol Mixtures-A Quasi-Elastic Neutron Scattering Study.

The solvent dynamics of concentrated solutions of poly(N-isopropylacrylamide) (PNIPAM, 25 wt %) in water/methanol mixtures (85:15 v/v) are measured with the aim of shedding light onto the cononsolvency effect. Quasi-elastic neutron scattering (QENS) with contrast variation has been carried out at temperatures below and above the cloud point by using in the first set of experiments the mixture H2O:d-MeOD (d-MeOD denotes fully deuterated methanol) as a solvent and in the second set of experiments the mixture D2O:MeOH (MeOH denotes methanol). As a reference, bulk H2O, bulk MeOH and the mixtures H2O:d-MeOD and D2O:MeOH (both 85:15 v/v) have been investigated as well. In the PNIPAM solution in H2O:d-MeOD, two water populations are identified, namely strongly and less strongly arrested water. At the cloud point, the former is partially released from PNIPAM. The diffusion coefficient of the latter one is similar to the one in the water/methanol mixture, and its residence time decreases at the cloud point. The PNIPAM solution in D2O:MeOH reveals similar dynamics to the one in H2O:d-MeOD which may reflect that the dynamics of MeOH near the PNIPAM chain is similar to the one of H2O. The similarity may, however, partially be due to H/D exchange between D2O and MeOH. In both PNIPAM solutions, the mean-square displacement of the PNIPAM chain decreases gradually above the cloud point.

Effect of Isotacticity of Linear Poly(N-isopropylacrylamide) on its Gelation in Benzyl Alcohol

Thermoreversible gelation of three different isotactic linear poly(N-isopropylacrylamide) (PNIPAM)s having meso dyad (m) values 62, 68 and 81% has been observed in benzyl alcohol. All the gels were transparent in nature. SEM image of the dried gels showed fibrillar network morphology. Melting temperature of the gels gradually increased with the increase in the concentration. XRD data of dry polymers and their corresponding dry gels showed shifting in the peak positions. Rheological study showed that stronger gels were formed with increasing isotacticity of PNIPAM while lower isotactic sample exhibited typical polymer melt rheology. The formation of a plunge in the storage modulus as well as in the viscosity plot at the same frequency range indicates the reversible nature of the structure breaking/reformation under frequency sweep. Moreover, the mechanical strength of the gel decreased with increase in temperature. UV-Vis kinetic study also indicated the change in the conformation and aggregation of PNIPAM chains during gelation. Molecular modelling calculation showed that the number of solvent molecules involved in forming gel (polymer-solvent compound) decreased with the increase in the isotacticity of the polymer. Gelation rate of these gels was studied as a function of temperature, concentration and isotacticity using test-tube tilting method. It increased with the increase in the concentration and isoacticity of the polymer, and with the decrease in the temperature. Critical gelation concentration of the gel gradually increased with the decrease in the isotacticity and with the increase in the temperature. All these experimental results indicated that gelation occurs presumably through polymer-solvent compound formation. Thermoreversible gelation of different isotactic [meso diad (m) = 62, 68 and 81%] linear poly(N-isopropylacrylamide) (PNIPAM)s has been observed in benzyl alcohol. Gelation rate depends on temperature, concentration, and isotacticity of PNIPAM. SEM, XRD, rheology and UV-Vis studies, and molecular modelling support its formation presumably via polymer-solvent compound formation.

In Situ Synthesis of Thermoresponsive Polystyrene-b-poly(N-isopropylacrylamide)-b-polystyrene Nanospheres and Comparative Study of the Looped and Linear Poly(N-isopropylacrylamide)s

Well-defined triblock copolymer nanospheres of polystyrene-block-poly(N-isopropylacrylamide)-block-polystyrene (PS-b-PNIPAM-b-PS) containing a hydrophobic core of the polystyrene (PS) block and a looped corona of the thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) block were prepared by the bifunctional macro-RAFT agent mediated dispersion polymerization via polymerization-induced self-assembly. This synthesis affords the fine control on the chemical composition of the PS-b-PNIPAM-b-PS triblock copolymer and on the diameter of the triblock copolymer nanospheres. By precisely investigating the thermoresponse of the PS-b-PNIPAM-b-PS triblock copolymer nanospheres and the poly(N-isopropylacrylamide)-block-polystyrene (PNIPAM-b-PS) diblock copolymer nanospheres under the strictly similar conditions, it is found that the phase transition of the looped PNIPAM chains takes place at a lower temperature and within a narrower temperature range than that of the linear PNIPAM chains. We believe that the present...

Mesoscopic simulation of a micellar poly(N-isopropyl acrylamide)-b-(polyethylene oxide) copolymer system

In this article we studied the micellar formation of poly(N-isopropyl acrylamide)-b-polyethylene oxide (PNIPAM-b-PEO) copolymers in an aqueous system. From molecular simulations the dependence on temperature of the Flory–Huggins interaction parameter χ for PNIPAM and PEO in water is obtained and compared with available experimental results and values from other theoretical calculations. By means of dissipative particle dynamics (DPD) we then simulated the coil–globule transition for PNIPAM chains in water with a transition temperature of around 305 K. The simulations for PNIPAM-b-PEO copolymers showed that at room temperature the chains are miscible in an aqueous phase but with a temperature increase the system turns into micelles at T = 305 K. The change in micelle anisotropy due to a different ratio PNIPAM/PEO of chains is also analyzed. What is observed is that for large PEO the large number of dissolved PEO chains gives a large corona size and the micelle is not spherical but obloide and as the number of PNIPAM is increased the micelle acquires a spherical shape. As an important application we considered the system micelle-water/anionic liquid (1-butyl-3-methylimidazolium hexafluorophosphate [BMIM]+[PF6]−). By increasing the temperature of the system from 306 K it is shown that at T = 345 K there is a transfer of the micelle from water to the ionic liquid phase and this was due to the change in the relative affinity of PEO to water and ionic liquid expressed by the change in χ. All the simulation outcomes are qualitatively consistent with experimental results and thus to our knowledge we give the first set of χ values for the interaction between PNIPAM and water in a wide range of temperature values.

How does the anionic surfactant SDS affect the association of hydrophobically end-modified PNIPAM chains in aqueous solution?

The studies on the interaction between thermo-responsive polymer PNIPAM and various ionic surfactants have been extensively investigated in the past few years. Unfortunately, the role of the hydrophobic end-group which is inevitably introduced by the initiator or chain transfer agent was generally overlooked in related studies. In this work, to show the interplay between the hydrophobic end-group and the surfactant molecule, five n-dodecyl-terminated poly(N-isopropylacrylamide)s (PNIPAMs-C12H25) with different chain lengths were prepared by RAFT polymerization. The unambiguous molecular parameters were obtained by GPC, LLS, 1H-NMR and UV–Vis measurements. Further study on the association behaviors in SDS aqueous solutions showed that, these PNIPAM-C12H25 chains can form uniform spherical micelles accompanied with a trace amount of large irregular aggregates in pure water at 20 °C, and the size-molar mass relation of aggregates presents a scaling law. The addition of SDS could continuously weaken the association of these alkyl-terminated PNIPAMs, reflected in the decrease of average hydrodynamic radius (<Rh>) and average aggregation number (<Nagg>) of aggregates. Also, it could endow the PNIPAM chains the polyelectrolyte characteristics, reflected in the emergency of a slow relaxation mode in dynamic LLS measurement. More interestingly, the reversal of the dependence of cloud point on the chain length was observed at high SDS concentration, which may be attributed to the preferentially van der Waals interaction between the SDS dodecyl tail and the PNIPAM dodecyl chain end.

Thermo-sensitive complex micelles from sodium alginate-graft-poly(N-isopropylacrylamide) for drug release

Polymer micelles with environmentally sensitive properties have potential applications in biomedicine. In this paper, thermo-sensitive complex micelles assembled from biocompatible graft copolymers sodium alginate-graft-poly(N-isopropylacrylamide) (SA-g-PNIPAM) and divalent metal ions were prepared for controlled drug release. The polymer micelles had core-corona structure, which was constituted by metal ions (Ba2+, Zn2+, Co2+) cross-linked sodium alginate as the core and thermo-sensitive PNIPAM chains as the corona. Formation of polymer micelles was determined by Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and dynamic light scattering (DLS). The polymer micelles were observed as regular spheres with good polydispersity and excellent performance on drug encapsulation and release ability. The cumulative release of 5-fluorouracil (5-FU) from micelles was controlled by pH, ionic strength or temperature of surroundings. The superior properties of sensitive polymer micelles induced by metal ions are expected to be utilized in controlled drug delivery systems.

Concentration dependent effects of urea binding to poly(N-isopropylacrylamide) brushes: a combined experimental and numerical study.

The binding effects of osmolytes on the conformational behavior of grafted polymers are studied in this work. In particular, we focus on the interactions between urea and poly(N-isopropylacrylamide) (PNIPAM) brushes by monitoring the ellipsometric brush thickness for varying urea concentrations over a broad temperature range. The interpretation of the obtained data is supported by atomistic molecular dynamics simulations, which provide detailed insights into the experimentally observed concentration-dependent effects on PNIPAM-urea interaction. In particular, in the low concentration regime (cu ≤ 0.5 mol L(-1)) a preferential exclusion of urea from PNIPAM chains is observed, while in the high concentration regime (2 ≤ cu ≤ 7 mol L(-1)) a preferential binding of the osmolyte to the polymer surface is found. In both regimes, the volume phase transition temperature (Ttr) decreases with increasing urea concentration. This phenomenon derives from two different effects depending on urea concentration: (i) for cu ≤ 0.5 mol L(-1), the decrease of Ttr is explained by a decrease of the chemical potential of bulk water in the surrounding aqueous phase; (ii) for cu ≥ 2 mol L(-1), the lower Ttr is explained by the favorable replacement of water molecules by urea, which can be regarded as a cross-linker between adjacent PNIPAM chains. Significant effects of the concentration-dependent urea binding on the brush conformation are noticed: at cu = 0.5 mol L(-1), although urea is loosely embedded between the hydrated polymer chains, it enhances the brush swelling by excluded volume effects. Beyond 0.5 mol L(-1), the stronger interaction between PNIPAM and urea reduces the chain hydration, which in combination with cross-linking of monomer units induces the shrinkage of the polymer brush.

Injectable platform hydrogel for musculoskeletal regeneration

Event Abstract Back to Event Injectable platform hydrogel for musculoskeletal regeneration Abbey Thorpe1, Christine L. Le Maitre1 and Chris Sammon2 1 Sheffield Hallam University, Biomedical Research Centre, United Kingdom 2 Sheffield Hallam University, Materials and Engineering Research Institute, United Kingdom Introduction: We describe the utilisation of precipitation polymerisation of poly (N-isopropylacrylamide) (pNIPAM) at the surface of dispersed Laponite® platelets that resist aggregation and can be maintained for long periods of time as a low viscosity liquid. Whilst in this colloidal liquid state, live cells, small molecules or particles can easily be incorporated. Upon cooling to body temperature the pNIPAM chains spontaneously transform to the 'coil' conformation, establishing multiple physical interactions and leading to irreversible gel formation without further addition of reagents (Fig 1), indicating it is an ideal platform for numerous tissue regeneration applications. Typically aqueous pNIPAM solutions are free-flowing liquids at room temperature and upon heating above ~32oC they form weak gels. The incorporation of a crosslinker increases the mechanical strength of the gel but the material ceases to be a liquid at lower temperatures and cannot easily be injected. Here we show how the incorporation of different triggers into the hydrogel via the use of a suitable comonomer and/or the incorporation of additives such as hydroxyapatite can induce differentiation of human mesenchymal stem cells (hMSC) into bone, disc or cartilage dependant on target tissue. Methods: pNIPAM-Laponite® hydrogels were synthesised and the incorporation of comonomers and guest molecules were investigated to determine effects on setting temperature, mechanical properties and cellular behaviour. MSCs were incorporated in hydrogels with or without hydroxyapatite and investigated under hypoxic conditions to investigate differentiation towards osteoblasts and nucleus pulposus cells of the intervertebral disc. Results and Discussion: The solidified, mechanically robust pNIPAM-Laponite® hydrogels were shown to be fully biocompatible without the usual need for any purification steps and could be tailored to mechanically mimic a range of natural tissue types via the choice of comonomer and/or the incorporation of additives such as hyaluronic acid, hydroxyapatite. Tailored differentiation to osteoblast like cells or nucleus pulposus cells was successfully achieved over a 6 week time course, with appropriate deposition of matrix and marker expression (Fig 2). Conclusions: The relative simplicity and clinical convenience of the hydrogel synthesis method described here could provide an effective and minimally-invasive treatment platform for orthopaedic regenerative medicine. The ability to uniformly incorporate cells and other additives prior to injection and gelation opens up an extensive range of biological opportunities. In particular, the inherent low viscosity of the colloidal hydrogel enables application through fine bore needles minimising damage to the target tissues and enabling the hydrogel to fill micro fissures, which is not currently possible with existing hydrogel systems. The authors would like to thank EPSRC (EP/H000275/1, EP/I016473/1) for funding. Keywords: Cell Differentiation, Hydrogel, Regenerative Medicine, 3D scaffold Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: New Frontier Oral Topic: Regenerative medicine: biomaterials for control of tissue induction Citation: Thorpe A, Le Maitre CL and Sammon C (2016). Injectable platform hydrogel for musculoskeletal regeneration. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.00672 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Abbey Thorpe Christine L Le Maitre Chris Sammon Google Abbey Thorpe Christine L Le Maitre Chris Sammon Google Scholar Abbey Thorpe Christine L Le Maitre Chris Sammon PubMed Abbey Thorpe Christine L Le Maitre Chris Sammon Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.