Hybrid Self-Assembled Gel Beads for Tuneable pH-Controlled Rosuvastatin Delivery

This article describes the fabrication of new pH-responsive hybrid gel beads combining the polymer gelator calcium alginate with two different low-molecular-weight gelators (LMWGs) based on 1,3 : 2,4-dibenzylidene-d -sorbitol: pH-responsive DBS-COOH and thermally responsive DBS-CONHNH₂, thus clearly demonstrating that different classes of LMWG can be fabricated into gel beads by using this approach. We also demonstrate that self-assembled multicomponent gel beads can be formed by using different combinations of these gelators. The different gel bead formulations exhibit different responsiveness – the DBS-COOH network can disassemble within those beads in which it is present upon raising the pH. To exemplify preliminary data for a potential application for these hybrid gel beads, we explored aspects of the delivery of the lipid-lowering active pharmaceutical ingredient (API) rosuvastatin. The release profile of this statin from the hybrid gel beads is pH-dependent, with greater release at pH 7.4 than at pH 4.0 – primary control of this process results from the pK_a of the API. The extent of pH-mediated API release is also significantly further modified according to gel bead composition. The DBS-COOH/alginate beads show rapid, highly effective drug release at pH 7.4, whereas the three-component DBS-COOH/DBS-CONHNH₂/alginate system shows controlled slow release of the API under the same conditions. These initial results indicate that such gel beads constitute a promising, versatile and easily tuned platform suitable for further development for controlled drug-delivery applications.     

Self-assembled gel tubes,filaments and 3D-printing with in situ metal nanoparticle formation and enhanced stem cell growth

This paper reports simple strategies to fabricate self-assembled artificial tubular and filamentous systems from a low molecular weight gelator (LMWG). In the first strategy, tubular ‘core–shell’ gel structures based on the dibenzylidenesorbitol-based LMWG DBS-CONHNH₂ were made in combination with the polymer gelator (PG) calcium alginate. In the second approach, gel filaments based on DBS-CONHNH₂ alone were prepared by wet spinning at elevated concentrations using a ‘solvent-switch’ approach. The higher concentrations used in wet-spinning prevent the need for a supporting PG. Furthermore, this can be extended into a 3D-printing method, with the printed LMWG objects showing excellent stability for at least a week in water. The LMWG retains its unique ability for in situ precious metal reduction, yielding Au nanoparticles (AuNPs) within the tubes and filaments when they are exposed to AuCl₃ solutions. Since the gel filaments have a higher loading of DBS-CONHNH₂, they can be loaded with significantly more AuNPs. Cytotoxicity and viability studies on human mesenchymal stem cells show that the DBS-CONHNH₂ and DBS-CONHNH₂/alginate hybrid gels loaded with AuNPs are biocompatible, with the presence of AuNPs enhancing stem cell metabolism. Taken together, these results indicate that DBS-CONHNH₂ can be shaped and 3D-printed, and has considerable potential for use in tissue engineering applications.

Simple fabrication and 3D-printing methods are used to generate tubes and filaments from self-assembled gels, which can be loaded in situ with gold nanoparticles, with the resulting gels encouraging stem cell proliferation.     

Self-Assembled Supramolecular Hybrid Hydrogel Beads Loaded with Silver Nanoparticles for Antimicrobial Applications

This Full Paper reports the formation of silver (Ag) NPs within spatially resolved two-component hydrogel beads, which combine a low-molecular-weight gelator (LMWG) DBS-CONHNH₂ and a polymer gelator (PG) calcium alginate. The AgNPs are formed through in situ reduction of Ag^I, with the resulting nanoparticle-loaded gels being characterised in detail. The antibacterial activity of the nanocomposite gel beads was tested against two drug-resistant bacterial strains, often associated with hospital-acquired infections: vancomycin-resistant Enterococcus faecium (VRE) and Pseudomonas aeruginosa (PA14), and the AgNP-loaded gels showed good antimicrobial properties against both types of bacteria. It is suggested that the gel bead format of these AgNP-loaded hybrid hydrogels makes them promising versatile materials for potential applications in orthopaedics or wound healing.     

Double diffusion for the programmable spatiotemporal patterning of multi-domain supramolecular gels

To achieve spatial resolution of a multi-component gel, a double diffusion approach is used which enables the precise programming of self-assembled patterned domains with well-defined shapes and sizes. The low-molecular-weight gelators (LMWGs) used in this study are pH-responsive DBS-CO₂H and thermally-responsive DBS-CONHNH₂ (both based on 1,3:2,4-dibenzylidenesorbitol, DBS). A DBS-CONHNH₂ gel was initially assembled in a tray, and then loaded at carefully-selected positions with either basified DBS-CO₂H (i.e. DBS-carboxylate) or an acid. These soluble components subsequently diffuse through the pre-formed gel matrix, and in the domains when/where they mix, protonation of the DBS-carboxylate induces self-assembly of the DBS-CO₂H network, leading to a patterned gel-in-gel object with well-defined shape and dimensions. Using a strong acid achieves fast gelation kinetics, creating smaller, better-defined macroscale objects but with less nanoscale order. Using a weak acid source with slow kinetics, gives slightly larger objects, but on the nanoscale the DBS-CO₂H network formation is better controlled, giving more homogeneous nanoscale structures and stiffer objects. The patterned objects can be further reinforced by the presence of agarose polymer gelator. The shape of the patterning is programmed by both the shape of the central reservoir and the starting geometry in which the reservoirs are organised, with the balance between factors depending on assembly kinetics, as dictated by the choice of acid. This simple methodology therefore enables programming of patterned gels with spatiotemporal control and emergent patterning characteristics.

To achieve spatial resolution of a multi-component gel, a double diffusion approach is used which enables the precise programming of emergent self-assembled patterned domains with well-defined shapes and sizes.     

Adsorption Studies of Copper Sulfate on Hydrogels of Poly(Amido-Amines)

Abstract

The interaction between the active groups of polymeric gels of poly(amido-amines) such as poly(acrylamide-diallyldiethyl ammonium chloride) “cationic gel p(AM-DADEAmCl)” and poly(acrylamide-sodium acrylate-diallyldiethyl ammonium chloride) “amphoteric gel p(AM-AANa-DADEAmCl” with copper sulfate have been carried out by using polymeric gels of different swelling degree and different amine percent.

The capacity toward cations decreases with increasing the amine percent and the swelling degree but the capacity toward anions such as (SO₄₎ ^2- decreases with increasing swelling degree and increases with increasing the amine percent. These polymeric gels interact with copper sulfate at pH value >5 to form a crosslinked structures. Spectroscopic studies showed that the mechanism of crosslinking formation is a bond formation between the active group of polymeric chains and copper sulfate. The bond formation depends on the nature of the polymer chain. It was also found that the amide groups form complexes with hydrated cations, while both carboxylate and ammonium groups interact by ion-exchange mechanisms.     

Fmoc-Dipeptide/Porphyrin Molar Ratio Dictates Energy Transfer Efficiency in Nanostructures Produced by Biocatalytic Co-Assembly

The controlled self-assembly of porphyrin derivatives (TCPP, tetrakis(4-carboxyphenyl)porphyrin) within Fmoc-protected (Fmoc=9-Fluorenylmethyloxycarbonyl) dipeptide (Fmoc-TL-NH₂) nanofibers is demonstrated. The biocatalytic co-assembly in aqueous medium generated an energy transfer hydrogel. Depending on the concentrations of porphyrin used, the resulting nanofibrous gels show two distinct regions of self-assembly behavior that is, integration of TCPP into nanostructures to produce two-component co-assembly fibers, or heterogeneous self-aggregation of TCPP within the self-assembled matrix observed at higher concentrations. The mode of assembly directly impacts on the energy transfer efficiency of these nanostructures. These results show that reversible biocatalytic co-assembly of structural and functional components enables fine-tuning of peptide/porphyrin energy transfer nanostructures.     

Heterogeneous polyelectrolyte gels as stimuli-responsive membranes

Stimuli-responsive membranes may act as “on–off switches” or “permeability valves”, producing patterns of pulsatile release, where the period and rate of mass transfer can be controlled by external or environmental triggers (e.g. pH, temperature, electric field). In this work, composite-heterogeneous polyelectrolyte gel (composite-HPG) membranes consisting of polymethacrylic acid (PMAA) gel particles dispersed within a polydimethylsiloxane (PDMS) network were developed and evaluated as pH-responsive membranes.The mechanism of permeability control for caffeine and vitamin B₁₂ through composite-HPG membranes was determined to be a synergistic function of membrane hydration and the percolating volume fraction of PMAA gel. Larger changes in permeation as a function of pH were achieved when both hydration and percolation effects occurred together than when either of these effects occurred on their own. Vitamin B₁₂ permeation was observed when the hydrated gel volume fraction was above approximately 0.38, but not below. Furthermore, the percolating fraction of composite-HPG membranes containing 28% (dry basis) PMAA gel particles was manipulated via pH to fall above (pH 7) or below (pH 3) this transition in permeability, resulting in membranes that delivered solutes of high molecular weight (vitamin B₁₂) with large on/off delivery ratios (160).     

Tunable two-component saccharide-based gels: The effect of the co-operation of two glucofuranose-based compounds having different gelating abilities

Addition of 1,2-O-(ethane-1,2-diyl)-α-d-glucofuranose, which is originally a poor organogelator, can support the gelating abilities of good glucofuranose-based organogelators. The properties of such two-component gels can be tuned by changing the proportion of the saccharides. The saccharide's ability to form two-component gels can be explained on the basis of its crystal structure, particularly, the way in which sugar molecules stack (or not) into hydrogen bond-based chains and the architecture of these chains. The thermal stability of the obtained two-component gels was characterised by measuring its T _gel temperature. SEM and XRD techniques were used to characterise the xerogels.

Addition of poor gelator increases the thermal stability of the gel formed by good gelator     

Synthesis of Fibrin-Type I Collagen Biomaterials via an Acidic Gel

Fibrin-Type I collagen composite gels have been widely studied as biomaterials, in which both networks are usually formed simultaneously at a neutral pH. Here, we describe a new protocol in which mixed concentrated solutions of collagen and fibrinogen were first incubated at acidic pH to induce fibrinogen gel formation, followed by a pH change to neutral inducing collagen fiber formation. Thrombin was then added to form fibrin-collagen networks. Using this protocol, mixed gels containing 20 mg.mL⁻¹ fibrin and up to 10 mg.mL⁻¹ collagen could be prepared. Macroscopic observations evidenced that increasing the content of collagen increases the turbidity of the gels and decreases their shrinkage during the fibrinogen-to-fibrin conversion. The presence of collagen had a minor influence on the rheological properties of the gels. Electron microscopy allowed for observation of collagen fibers within the fibrin network. 2D cultures of C2C12 myoblasts on mixed gels revealed that the presence of collagen favors proliferation and local alignment of the cells. However, it interferes with cell differentiation and myotube formation, suggesting that further control of in-gel collagen self-assembly is required to elaborate fully functional biomaterials.     

Photoinduced Energy- and Electron-Transfer Processes in a Side-to-Face RuII-Porphyrin/Perylene-bisimide Array

A side-to-face array DPy-gPBI[Ru(4-tBuTPP)(CO)]₂, based on a “green” perylene bisimide chromophore sandwiched between two Ru^II-porphyrins, has been prepared by self-assembly. Its photophysical properties have been characterized in detail by a combination of steady-state and time-resolved techniques upon selective excitation of the two different components. Different photoinduced processes are observed as a function of the excitation wavelength. Electron transfer quenching is attained upon “red light” excitation of the perylene unit, whilst an energy transfer pathway is followed upon “green light” excitation of the metallo-porphyrin moiety. Regardless of the excitation wavelength efficient population of the triplet excited state of the perylene chromophore is achieved. The photophysical results are discussed within the framework of classical electron transfer theory and compared with those of a previously reported system.     

Synthesis of polyoxovanadates via “chimie douce”

A large variety of new polyoxovanadates have been synthesized during the past few years by sol–gel chemistry or hydrothermal methods. These wet chemistry methods offer many advantages compared to the usual solid state syntheses. New open structures have been obtained from aqueous precursors. They result from the self-assembling of ionic species in the solution.Vanadium oxide gels and sols, V₂O₅·nH₂O, are formed around the point of zero charge (pH≈2). They have a ribbon-like structure and exhibit a liquid crystal behavior. These mesophases are similar to those currently observed with nematic polymers. Xerogel layers deposited from V₂O₅·nH₂O gels exhibit some preferred orientation and behave as versatile host structures for intercalation giving new hybrid organic–inorganic nanocomposites.Layered structures are formed around pH≈7 in the presence of large organic cations. They are built of mixed valence polyoxovanadate planes made of [VO₅] pyramids and [VO₄] tetrahedra. Organic cations lie between the oxide layers where they interact with the negative oxygen of the VO double bonds.Anions can behave as templating agents. Hollow cluster shells are formed around anions that remain encapsulated within the negatively charged polyvanadate cage. Large cations only behave as counter ions for the formation of a neutral crystalline network.It appears that the molecular structure of V^V precursors depends mainly on pH, but the way they self-assemble may be governed by other ionic species in the solution.     

Primary Ammonium Monocarboxylate Synthon in Designing Supramolecular Gels: A New Series of Chiral Low‐Molecular‐Weight Gelators Derived from Simple Organic Salts that are Capable of Generating and Stabilizing Gold Nanoparticles

The primary ammonium monocarboxylate (PAM) synthon has been exploited to generate a new series of PAM salts from the free amine of L ‐phenylalanine‐3‐pyridyl amide, (S)‐2‐amino‐3‐phenyl‐N‐(pyridine‐3‐yl)propanamine (designated as “ B ”), and various substituted benzoic acids (designated as “ A(R) ”; R =4‐Me, 4‐Cl, 4‐Br, 4‐NO₂, 3‐Me, 3‐Cl, 3‐Br, 3‐NO₂, 2‐Me, 2‐Cl, 2‐Br, 2‐NO₂). The 4‐ and 3‐substituted benzoate salts showed moderate‐to‐excellent gelation ability with a number of polar and apolar solvents. The gels were characterized by DSC, rheology, SEM and TEM, FTIR spectroscopy, etc. Structure–property studies based on single‐crystal powder X‐ray diffraction (PXRD) and FTIR data provided insights into the role of the PAM synthon in the formation of the gel networks. Interestingly, some of the gels were capable of forming and stabilizing gold nanoparticles at room temperature without the use of any exogenous reducing agents.     

Preparation of Forsterite by the Geopolymer Technique—Gel Compositions as a Function of pH and Crystalline Phases

Mg-bearing silicate precursor gels have been prepared by mixing 0.74 mol/L sodium metasilicate and 1.48 mol/L magnesium nitrate solutions. Caustic soda solution of 1.0 mol/L concentration was introduced to regulate pH. The magnesium nitrate solution was added dropwise to the sodium silicate solution in equi-volume at various pH values. Raw and heat-treated gels were characterized by XRF, TG-DTA, XRD and FE-SEM. As a result, gel compositions were dependent on pH values of mixing solutions. The pH value yielding stoichiometric forsterite composition, MgO/SiO₂ = 2 was reached at pH 9.3. In addition, this value was pH 8.4 for stoichiometric enstatite composition, MgO/SiO₂ = 1. With decreasing pH from 9.3, the ratio became less than 2 and forsterite and enstatite precipitated by heating the gels. With increasing pH from 9.3, the ratio became more than 2 and forsterite and periclase precipitated by heating the gels. DTA curves showed a characteristic exothermic peak centered at 700–900^∘C, indicating relatively low temperature formation of crystalline phases due to the presence of polycondensed frame works of silicates in the precursor gels.     

Synthesis of transition‐metal‐ion‐selective poly(N‐isopropylacrylamide) hydrogels by the incorporation of an Aza crown ether

A functionalized cyclam was synthesized by the attachment of a polymerizable acryloyl group to one of the four nitrogens on the cyclam molecule. The polymerization of the functionalized cyclam was performed with N‐isopropylacrylamide and N,N′‐methylene bisacrylamide, and the gels obtained were studied in the presence of different transition‐metal‐ion solutions. There was a drastic difference in the phase‐transition temperature (T_c) of the poly(N‐isopropylacrylamide) (PNIPAAm)/cyclam gel in comparison with the pure PNIPAAm gel. For the described system, a T_c shift of 15 °C was obtained. The presence of functionalized cyclam increased the hydrophilicity and T_c of the aforementioned polymer gels in deionized water (at pH 6) because of the presence of protonated amino moieties. The PNIPAAm/cyclam gels showed a dependence of the swelling behavior on pH. T_c of the pure PNIPAAm gel was weakly influenced by the presence of any transition‐metal ions, such as Cu²⁺, Ni²⁺, Zn²⁺, and Mn²⁺. The addition of Cu²⁺ or Ni²⁺ to the PNIPAAm/cyclam gel reduced T_c of the polymer gel, and a shift of approximately 12 °C was observed. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 1594–1602, 2003     

Organogel of fluorescein-based derivative formation in the selected pH value

In this work, film structure was obtained by self-assembly of fluorescein derivative via sol–gel process. The self-assembly structure and the formation mechanism had been studied and certified by scanning electron microscopy, IR, UV–vis, fluorescence and X-ray diffraction experiment data. The UV–vis absorption and emission spectra of the compound 1 were changed with the change of the pH value in the solution state. This gelator had certain selectivity for pH value and formed gels.     

Construction of triblock copolymer-gold nanorod composites for fluorescence resonance energy transfer via pH-sensitive allosteric

To explore the effects of microenvironmental adjustments on fluorescence, a pH-sensitive nanocomposite system based on fluorescence resonance energy transfer (FRET) was constructed. The model system included a modified triblock copolymer (polyhistidine-b-polyethylene glycol-b-polycaprolactone) and gold nanoparticles. A near-infrared dye was used as the donor, and spectrally matched gold nanorods, attached after C-terminus modification with α-lipoic acid, were used as the receptor to realize control of the FRET effect over the fluorescence intensity for two polymer configurational changes (i.e., “folded” and “stretched” states) in response to pH. After synthesis and characterization, we investigated the self-assembly behavior of the system. Analysis by quartz crystal microbalance revealed the pH sensitivity of the polymer, which exhibited “folding” and “stretching” states with changes in pH, providing a structural basis for the FRET effect. Fluorescence spectrophotometry investigations also revealed the regulatory impact of the assembled system on fluorescence.     

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

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

Preparation of an intelligent hydrogel sensor based on g-C3N4 nanosheets for selective detection of Ag+

In this study, an “intelligent” graphitic carbon nitride nanosheets/ polyacrylamide/ polyacrylic acid (CNNS/ PAM/ PAA) composite hydrogel was prepared by radical polymerization method. The structure, swelling and fluorescent properties of the gels were investigated. The results showed that the mixed gel not only had pH sensitivity in aqueous solution, but also had specific concentration-dependent fluorescent intensities in the presence of Ag⁺ over the range (0–100) μM with a detection limit of 6.31 μM. The mixed gel can be applied to be fluorescence probe for detection of Ag⁺.     

Multiresponsive Viscoelastic Vesicle Gels of Nonionic C12EO4 and Anionic AzoNa

Viscoelastic vesicle gels were prepared by mixing a nonionic surfactant, tetraethylene glycol monododecyl ether (C₁₂EO₄), and an anionic dye, sodium 4‐phenylazobenzoic acid (AzoNa). The gels, which were composed of multilamellar vesicles, were analyzed by cryogenic transmission electron microscopy (cryo‐TEM), freeze–fracture transmission electron microscopy (FF‐TEM), ²H NMR spectroscopy, and small‐angle X‐ray scattering (SAXS). The mechanism of vesicle‐gel formation is explained by the influence of anionic molecules on the bilayer bending modulus. Interestingly, the vesicle gels were observed to be sensitive to temperature, pH, and light. The viscoelastic vesicle gels respond to heat; they thin at lower temperatures and become thicker at higher temperatures. The vesicle gels are only stable from pH 7 to 11, and the gels become thinner outside of this range. UV light can also trigger a structural phase transition from micelles to multilamellar vesicle gels.