Amphiphilic Networks Research Articles

Impact of Swelling on Macroscopic and Nanoscopic Mechanical Properties of Amphiphilic Polymer Co‐Networks in Non‐Selective and Selective Solvents

AbstractAmphiphilic polymer gels show environmentally sensitive mechanical properties depending on the solvent polarity, which makes them useful for applications in soft contact lenses, membranes, drug delivery systems, and tissue engineering. To rationally design the material properties for such applications, a sound knowledge about the mechanical properties at different solvency states is necessary. To acquire such knowledge, amphiphilic networks are prepared by hetero‐complementary coupling of amine‐terminated tetra‐poly(ethylene glycol) (t‐PEG‐NH2) with 2‐(4‐nitrophenyl)‐benzoxazinone terminated tetra‐poly(ε‐caprolactone) (t‐PCL‐Ox). The mechanical properties are investigated on different length‐scales and under non‐selective and selective solvent conditions using shear rheometry and atomic force microscopy (AFM). The swelling as well as the modulus in good solvent are in accord with scaling laws found for other four‐arm star‐shaped polymer networks and theoretical predictions. The swelling in selective solvent reveals a concentration‐independent volume swelling degree and a nearly linear scaling of the modulus with concentration. The surface topography probed by AFM reveals microphase‐separated structures in the range of 20 nm. Similar modulus values are obtained for bulk films in water using the complementary methods of atomic force microscopy and rheometry. The data are compared with pure hydrophilic networks to identify the effect of amphiphilicity on the material properties.

Stereo-Complex and Click-Chemical Bicrosslinked Amphiphilic Network Gels with Temperature/pH Response.

Stimulus-responsive hydrogels have been widely used in the field of drug delivery because of their three-dimensional pore size and the ability to change the drug release rate with the change in external environment. In this paper, the temperature-sensitive monomer 2-methyl-2-acrylate-2-(2-methoxyethoxy-ethyl) ethyl ester (MEO2MA) and oligoethylene glycol methyl ether methacrylate (OEGMA) as well as the pH-sensitive monomer N,N-Diethylaminoethyl methacrylate (DEAEMA) were used to make the gel with temperature and pH response. Four kinds of physicochemical double-crosslinked amphiphilic co-network gels with different polymerization degrees were prepared by the one-pot method using the stereocomplex between polylactic acid as physical crosslinking and click chemistry as chemical crosslinking. By testing morphology, swelling, thermal stability and mechanical properties, the properties of the four hydrogels were compared. Finally, the drug release rate of the four gels was tested by UV-Vis spectrophotometer. It was found that the synthetic hydrogels had a good drug release rate and targeting, and had great application prospect in drug delivery.

Construction of amphiphilic networks in blend membranes for CO2 separation

Construction of amphiphilic networks in blend membranes for CO2 separation

Covalent segmented polymer networks composed of poly(2-isopropenyl-2-oxazoline) and selected aliphatic polyesters: designing biocompatible amphiphilic materials containing degradable blocks.

To promote facile and efficient synthesis of segmented covalent networks, we developed a cross-linking process with reactive polymeric components in a system without catalysts or side products. To achieve the direct formation of amphiphilic networks, an addition reaction was performed between the polyesters containing carboxyl terminal groups with pendant groups distributed along poly(2-isopropenyl-2-oxazoline) chains. Covalent cross-linking was achieved from predetermined amounts of components dissolved in DMSO at 140 °C. To tune the properties of the resulting networks, the composition and length of the polyester segments and the degree of cross-linking were changed in the feed. The chemical structure of the networks was characterized using Fourier transform infrared-attenuated total reflection spectroscopy and 13C magic-angle spinning NMR. The swelling ability of the formed networks was investigated in aqueous and organic media. Moreover, mechanical properties were tested during uniaxial compression. The cytocompatibility of the scaffolds was confirmed by MTT assay. Through the results obtained, the first report describing the cross-linking of polyesters on hydrophilic PiPOx was provided to prepare new, biocompatible materials with tuneable properties that are promising for potential biomedical applications.

Synthesis of New Type Polymers by Quasi-Living Atom Transfer Radical Polymerization.

Thanks to the polymer revolution of the 20th century, plastics are now part of our everyday lives. We use plastics as naturally as if they had always been an integral part of our lives. However, in the recent past, we were still predominantly using wood, metal, and glass objects, which were replaced by plastic products at an explosive rate. In many cases, this replacement has resulted in products with better physical, chemical, or biological properties. The changeover was too rapid, and the consequences were not recognized in time. This is evidenced by the huge scale of plastic pollution worldwide today. It is therefore in the interests of the future of both humans and animals that we must pay particular attention to the direct and indirect environmental impact of plastics introduced in animal husbandry. Starting from the tetrafunctional initiator produced as the first step of my work, poly(n-butyll acrylate) star polymers of different molecular weights were synthesized by atom transfer radical polymerization, using the so-called “core first” method. The bromine chain end of the produced star polymers was replaced by an azide group using a substitution reaction. Propalgyl telechelic PEGs were synthesized as a result of lattice end modification of poly(ethylene glycol) with different molecular weights. The azidated star polymers were connected with propalgyl telechelic PEGs using Huisgen’s “click” chemical process, and as a result of the “click” connection, amphiphilic polymer networks with several different structures were obtained.

Dual-reactive nanogels for orthogonal functionalization of hydrophilic shell and amphiphilic network.

Amphiphilic nanogels (NGs) combine a soft, water-swollen hydrogel matrix with internal hydrophobic domains. While these domains can encapsulate hydrophobic cargoes, the amphiphilic particle surface can reduce colloidal stability and/or limit biological half-life. Therefore, a functional hydrophilic shell is needed to shield the amphiphilic network and tune interactions with biological systems. To adjust core and shell properties independently, we developed a synthetic strategy that uses preformed dual-reactive nanogels. In a first step, emulsion copolymerization of pentafluorophenyl methacrylate (PFPMA) and a reduction-cleavable crosslinker produced precursor particles for subsequent network modification. Orthogonal shell reactivity was installed by using an amphiphilic block copolymer (BCP) surfactant during this particle preparation step. Here, the hydrophilic block poly(polyethylene glycol methyl ether methacrylate) (PPEGMA) contains a reactive alkyne end group for successive functionalization. The hydrophobic block (P(PFPMA-co-MAPMA) contains random methacryl-amido propyl methacrylamide (MAPMA) units to covalently attach the surfactant to the growing PPFPMA network. In the second step, orthogonal modification of the core and shell was demonstrated. Network functionalization with combinations of hydrophilic (acidic, neutral, or basic) and hydrophobic (cholesterol) groups gave a library of pH- and redox-sensitive amphiphilic NGs. Stimuli-responsive properties were demonstrated by pH-dependent swelling and reduction-induced degradation via dynamic light scattering. Subsequently, copper-catalyzed azide-alkyne cycloaddition was used to attach azide-modified rhodamine as model compound to the shell (followed by UV-Vis). Overall, this strategy provides a versatile platform to develop multi-functional amphiphilic nanogels as carriers for hydrophobic cargoes.

Amphiphilic Nanogels: Fuzzy Spheres with a Pseudo-Periodic Internal Structure.

Amphiphilic polymer nanogels (NGs) are promising drug delivery vehicles that extend the application of conventional hydrophilic NGs to hydrophobic cargoes. By randomly introducing hydrophobic groups into a hydrophilic polymer network, loading and release profiles as well as surface characteristics of these colloids can be tuned. However, very little is known about the underlying internal structure of such complex colloidal architectures. Of special interest is the question how the amphiphilic network composition influences the internal morphology and the "fuzzy" surface structure. To shine light into the influence of varying network amphiphilicity on these structural features, we investigated a small library of water-swollen amphiphilic NGs using small-angle X-ray scattering (SAXS). It was found that overall hydrophilic NGs, consisting of pure poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA), display a disordered internal structure as indicated by the absence of a SAXS peak. In contrast, a SAXS peak is present for amphiphilic NGs with various amounts of incorporated hydrophobic groups such as cholesteryl (CHOLA) or dodecyl (DODA). The internal composition of the NGs is considered structurally homologous to microgels. Application of the Teubner-Strey model reveals that hydrophilic PHPMA NGs have a disordered internal structure (positive amphiphilicity factor) while CHOLA and DODA samples have an ordered internal structure (negative amphiphilicity factor). From the SAXS data it can be derived that the internal structure of the amphiphilic NGs consists of regularly alternating hydrophilic and hydrophobic domains with repeat distances of 3.45-5.83 nm.

Utilization of a fattigation platform gelatin-oleic acid sodium salt conjugate as a novel solubilizing adjuvant for poorly water-soluble drugs via self-assembly and nanonization.

Solubilizing adjuvants are commonly used to dissolve insoluble drugs by simply adding in a formulation. In this study, gelatin and oleic acid sodium salt (OAS), a generally recognized as safe-listed material were chosen and conjugated to develop a natural solubilizing adjuvant using the fattigation platform technology to enhance solubility and dissolution rate of poorly water-soluble drugs according to self-assembly and nanonization principle when simply mixed with poorly water-soluble drugs. We synthesized the gelatin and OAS conjugates (GOC) at three different ratios (1:1, 1:3, 1:5; GOC 1, GOC 2, and GOC 3, respectively) via the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide reaction using a spray dryer. This amphiphilic micronized GOC was self-assembled into nanoparticles. The synthesis of new amphiphilic conjugates was identified through Fourier transform-infrared (FT-IR) spectroscopy. The powder properties of the GOCs, such as angle of repose, bulk density, and tapped density were varied with the oleic acid bonding ratio. Then, GOCs were utilized to investigate the enhanced solubility and release rate of various poorly water-soluble drugs such as cilostazol (CSZ), coenzyme Q10, ticagrelor, telmisartan, aprepitant and itraconazole as model drugs. Based on the solubility studies by concentration and type of GOCs, 3% GOC 2 was selected. When this GOC was mixed with these model drugs by the physical mixing, wetting and hot melting methoods, the solubility was highly enhanced compared to the pure control drug, ranging from 20 to 150,000 times. In case of CSZ, all formulations were significantly improved release rate compared to the of CSZ alone and the reference tablet, cilostan® (Korea United Pharm) in simulated intestinal fluid containing 0.2% sodium lauryl sulfate. Differential scanning calorimetry and powder X-ray diffraction were conducted to confirm the crystal polymorphic structure of CSZ, and as a result they changed to diminutive peak intensity compared to CSZ alone. Field-emission scanning electron microscopy indicated that GOC was round with a reduced size of about 100nm. The reduction of drug particles via nanonization and self-assembly of amphiphilic GOC in an aqueous media could be a key factor to improve poor water solubility by providing a favorable dispersion of drug molecules in an amphiphilic network.

Direct formation of amphiphilic crosslinked networks based on PVP as a marine anti-biofouling coating

In this work, we developed a novel amphiphilic coating by incorporating poly (N-vinylpyrrolidone) (PVP), a highly hydrophilic polymer with strong physicochemically stability, into polydimethylsiloxane (PDMS) matrix. PVP was firstly functionalized with triethoxysilane and then directly crosslinked with PDMS to form an amphiphilic network coating at room temperature. Results suggested that the hydrophilicity of PDMS matrix was significantly improved after the modification. Moreover, compared to pristine PDMS, PDMS-PVP coatings could efficiently prevent the adhesion of bacteria and Navicula diatoms (both 99% reduction), as well as resist the attachment of mimetic barnacle (82% reduction). More importantly, PDMS-PVP coatings also showed excellent anti-biofouling performance for at least 4 months in the marine field tests. This work provides a novel strategy to prepare high-performance anti-biofouling coatings, which are expected to advance the development of environmentally-friendly coatings in marine applications.

Poly(ethylene glycol)‐based amphiphilic networks and their swelling properties

AbstractNew amphiphilic networks were generated using the various molecular mass of poly (ethylene glycol) and 1,8‐bis(triethoxysilyl) octane through an easy polycondensation process at relatively high temperature to use as a sorbent material. The characterization of obtained sorbents was managed using Fourier‐transform infrared spectroscopy, 13C, and 29Si cross‐polarization magic angle spinning nuclear magnetic resonance, and thermal properties were settled by thermogravimetric analysis. Swelling skill of the sorbents was specified by swelling tests using several organic solvents such as dichloromethane (DCM), tetrahydrofuran, methyl tertiary butyl ether, toluene, and water due to its amphiphilic nature. Synthesized sorbents show quite large amount of organic solvent absorption for instance 1,800% in DCM with excellent reusability up to 10 cycles and have good strength against hydrolysis from 96 to 168 hr in water according to structure of obtained sorbents.

The Study of Formation of Amphiphilic Network Block Copolymer of N-Isopropylacrylamide

The regularities of formation of the structure of amphiphilic network copolymers on radical copolymerization of N-isopropylacrylamide and polyester dimethacrylate are investigated. The kinetic laws of the consumption of functional groups and the increase in the gel content during formation of a crosslinked product are studied. It is shown that the synthesis of crosslinked amphiphilic copolymers proceeds via competing reactions of N-isopropylacrylamide homopolymerization and its copolymerization with polyester dimethacrylate. With the excess of the monofunctional monomer, a homogeneous rubber-like network copolymer is formed, whereas the excess of the bifunctional reagent results in the morphological inhomogeneity of the reaction product.

Influence of silicone distribution and mobility on the oxygen permeability of model silicone hydrogels

In order to understand the influence of composition on oxygen permeability, the morphology of model silicone hydrogels in both the dry and hydrated states was characterized using a variety of techniques (AFM, HAADF-STEM, solid-state NMR, and X-ray scattering). The model system studied is heterogeneous on length scales below 20 nm and consists of globular silicone-rich domains that rearrange in response to changes in hydration. In contrast to the well-defined morphologies of block copolymer systems, these radically cured amphiphilic networks are less ordered, showing gradual composition fluctuations. Comprehensive morphology characterization rationalizes the transport behavior of these heterogeneous hydrogels: the non-linear permeability increase with increasing silicone monomer content is not only related to changes in the spatial arrangement of silicone-rich domains but also to their mobility. This understanding is needed for further optimizing soft contact lens materials where oxygen transport and optical clarity are critical features.

In Situ FT-IR Spectroscopy Investigation of the Water Sorption of Amphiphilic PDMS Crosslinked Networks

An amphiphilic poly(dimethyl siloxane) (PDMS) network is obtained by incorporation of poly(ethylene glycol) hydrophilic side chains within the hydrophobic matrix with the objective of improving the water affinity characteristics of the unmodified PDMS network. Sorption of water as a function of relative pressure of water vapor is investigated by in situ Fourier-transform infrared (FT-IR) spectroscopy. This experimental technique supplies information on the molecular interaction established between the penetrant and the polymer substrate and identifies the occurrence of self-association between water molecules (clustering). Self-association of penetrant increases with the concentration of water in the amphiphilic network. The overall diffusivity slightly decreases with increasing water concentration, likely due to the clustering effect. The maximum amount of water sorbed at equilibrium is low (<0.3 wt%), but significantly larger than that of the unmodified network.

Semi-Interpenetrating Polymer Networks with Predefined Architecture for Metal Ion Fluorescence Monitoring.

The development of new synthetic approaches for the preparation of efficient 3D luminescent chemosensors for transition metal ions receives considerable attention nowadays, owing to the key role of the latter as elements in biological systems and their harmful environmental effects when present in aquatic media. In this work, we describe an easy and versatile synthetic methodology that leads to the generation of nonconjugated 3D luminescent semi-interpenetrating amphiphilic networks (semi-IPN) with structure-defined characteristics. More precisely, the synthesis involves the encapsulation of well-defined poly(9-anthrylmethyl methacrylate) (pAnMMA) (hydrophobic, luminescent) linear polymer chains within a covalent poly(2-(dimethylamino)ethyl methacrylate) (pDMAEMA) hydrophilic polymer network, derived via the 1,2-bis-(2-iodoethoxy)ethane (BIEE)-induced crosslinking process of well-defined pDMAEMA linear chains. Characterization of their fluorescence properties demonstrated that these materials act as strong blue emitters when exposed to UV irradiation. This, combined with the presence of the metal-binding tertiary amino functionalities of the pDMAEMA segments, allowed for their applicability as sorbents and fluorescence chemosensors for transition metal ions (Fe3+, Cu2+) in solution via a chelation-enhanced fluorescence-quenching effect promoted within the semi-IPN network architecture. Ethylenediaminetetraacetic acid (EDTA)-induced metal ion desorption and thus material recyclability has been also demonstrated.

Dynamic Anti-Icing Coatings: Complex, Amphiphilic Hyperbranched Fluoropolymer Poly(ethylene glycol) Cross-Linked Networks with an Integrated Liquid Crystalline Comonomer

Amphiphilic hyperbranched fluoropolymer coatings incorporating liquid crystalline moieties and poly(ethylene glycol) cross-linkers were found to demonstrate noteworthy anti-icing properties. A series of amphiphilic networks was synthesized through variation of the polymer molecular weights and hydrophilic/hydrophobic component ratios. These innovative materials show a remarkable reduction in the free water melting transition (Tm) temperature (−10 °C), measured by differential scanning calorimetry, and an increase in water contact angle for dry and water-swollen systems. The addition of this ordered parameter generated a unique coating topography, which can be visualized via polarized optical microscopy and 3D optical microscopy, while maintaining an overall macroscopic homogeneity.

Curcumin-encapsulating Nanogels as an Effective Anticancer Formulation for Intracellular Uptake.

Nanoscale drug delivery systems represent an attractive strategy to improve both the efficacy and safety of anticancer drugs. In this work, we describe nanoformulation of curcumin, a most potent natural anticancer compound capable of killing cancer cells while sparing the normal tissues. Since curcumin is a natural hydrophobic polyphenol, it has a low aqueous solubility and bioavailability, which are challenging to its therapeutic efficacy. We developed and evaluated a novel colloidal nanogel carrier for encapsulation of curcumin to increase its solubility and cytotoxicity. Amphiphilic Poloxamer-cationic network in the nanogel NG127 was designed to efficiently encapsulate curcumin. Homogenous drug complexes were obtained with 20-25% content of curcumin and the particle size of ca. 150 nm. Using ImageStream multispectral imaging flow cytometry, we demonstrated that the curcumin-nanogel formulation (C-NG) was readily internalized into MDA-231 breast cancer cells. A real-time cell growth electronic sensing assay was used to measure proliferation responses of various breast cancer cells to C-NG treatments. Our results indicated that the C-NG formulation was 70-85% more effective in inhibiting growth, at concentrations lower than IC50 of free curcumin. This was also confirmed morphologically by modified acridine orange/ethidium bromide staining and fluorescent microscopy. Importantly, nanocarrier NG127 alone displayed practically no cytotoxicity. We conclude that nanogel carriers offer an innovative way to encapsulate curcumin and to obtain more effective anticancer therapeutics than curcumin alone with a potential to specific tumor targeting, such as using antibodies against surface receptors specific to breast cancer cells.

Amphiphilic single and double networks: a small-angle X-ray scattering investigation

We investigated the microphase-separated morphologies of water-swollen amphiphilic single and double polymer networks using small-angle X-ray scattering (SAXS). The networks consist of (i) a first conetwork containing hydrophobic blocks from either 2-ethylhexyl methacrylate (EHMA) or lauryl methacylate (LauMA) and hydrophilic blocks from 2-(dimethylamino)ethyl methacrylate (DMAEMA) and (ii) a second polyacrylamide (PAAm) network. The SAXS curves are modeled by spherical core-shell micelles, where densely packed hydrophobic cores are surrounded by swollen hydrophilic chains. The correlation between these hydrophobic cores is described using a hard-sphere structure factor. A Porod law and an Ornstein-Zernike structure factor are adopted to capture the strong forward scattering due to large-scale inhomogeneities and the correlation between polymer strands, respectively. The size of the hydrophobic cores depends on the degree of polymerization of the hydrophobic block: for medium and long hydrophobic blocks, several hydrophobic cores merge together to form a larger core. When the second PAAm network is present, the nanostructures of the first amphiphilic network are less well-defined.

Forced blending of poly(5-vinyltetrazole) with vinyl polymers

An approach to the forced blending of poly(5-vinyltetrazole) with carbon backbone epoxy polymers of various types through the formation of interpolymers has been considered. The covalent bonding of macromolecules of dissimilar polymers is the result of alkylation of unsubstituted N–H tetrazole fragments by oxirane cycles of the second participant of the reaction. Some properties of the resulting amphiphilic network interpolymers have been studied.

The properties of network interpolymers with caprolactam and tetrazole cycles

On the basis of poly(5-vinyltetrazole) and the copolymer N-vinylcaprolactam–2-(vinyloxyethoxy)methyloxirane, amphiphilic network paired polymers capable of limited swelling in aqueous media with the formation of polyelectrolyte hydrogels characterized by pH sensitivity and thermal sensitivity have been obtained.

From Membrane to Skin: Aqueous Permeation Control Through Light‐Responsive Amphiphilic Polymer Co‐Networks

The functionalization of amphiphilic polymer co‐networks with light‐responsive spiropyran and spirooxazine derivatives leads to a new type of light‐responsive materials. The material consisting of hydrophilic nanochannels shows desirable properties such as light‐responsive permeability changes of aqueous caffeine solutions, an exceptional repeatability of the photochromism, and tunable basic permeability rates. The versatility of the system is demonstrated by using different functionalization routes such as copolymerization of light‐responsive monomers or crosslinker as well as postmodification of the preformed amphiphilic network. Moreover, light‐responsive spirobenzopyran and novel spirooxazine derivatives are synthesized, which changes the properties of the light‐responsive membranes after inclusion into the amphiphilic co‐networks. Finally, the permeability of the delivery membrane can be tailored to match the properties of porcine skin, an in vitro model of human neonatal skin. One possible application might be the use of the light‐responsive membranes as key‐unit of a transdermal caffeine‐delivery system for preterm neonates.