Tunable supramolecular hydrogel for in situ encapsulation and sustained release of bioactive lysozyme

To develop new matrices for the entrapment and sustained release of bioactive lysozyme, a series of supramolecular hydrogels based on α-cyclodextrin (α-CD) and water-soluble poly(ε-caprolactone)-poly(ethylene glycol) block copolymer (PCL-b-PEG) were prepared in the presence of chicken egg lysozyme. Different from commonly used polymeric microspheres and chemically crosslinked hydrogels for lysozyme encapsulation, such hydrogel matrices could be formed under mild conditions without high temperature and the use of chemical emulsifiers or crosslinkers. Their gelation rate, mechanical strength and shear viscosity as well as the release behavior for the encapsulated lysozyme could be tuned easily by the change of α-CD or PCL-b-PEG amount. For the encapsulated lysozyme, its conformation and biological activity could be well maintained when compared to native lysozyme. For the resultant supramolecular hydrogels, they were also confirmed to have a good biocompatibility by MTT assay using mice skin fibroblast (L929).     

A novel route to in‐situ incorporation of silver nanoparticles into supramolecular hydrogel networks

A novel strategy was developed for the in situ incorporation of silver nanoparticles into the supramolecular hydrogel networks, in which colloidally stable silver hydrosols were firstly prepared in the presence of an amphiphilic block copolymer of poly(oxyethylene)‐poly(oxypropylene)‐poly(oxyethylene) and then mixed with aqueous solution of α‐cyclodextrin. The analyses from rheology, X‐ray diffraction, and scanning electron microscopy confirmed the formation of the supramolecular‐structured hydrogels hybridized with silver nanoparticles. In particular, the colloidal stability of the resultant silver hydrosol and its gelation kinetics in the presence of α‐cyclodextrin as well as the viscoelastic properties of the resultant hybrid hydrogel were investigated under various concentrations of the used block copolymer. It was found that the used block copolymer could act not only as the effective reducing and stabilizing agents for the preparation of the silver hydrosol but also as the effective guest molecule for the supramolecular self‐assembly with α‐cyclodextrin. In addition, the effects of silver nanoparticles on the gelation process and the hydrogel strength were also studied. Such a hybrid hydrogel material could show a good catalytic activity for the reduction of methylene blue dye by sodium borohydride. © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 740–749, 2009     

PELGE nanoparticles as new carriers for the delivery of plasmid DNA

Biodegradable monomethoxy(polyethyleneglycol)-poly(lactide-co-glycolide)-monomethoxy(poly-ethyleneglycol) (PELGE) copolymers were synthesized by ring-opening polymerization to formulate plasmid DNA loaded nanoparticles. A double emulsion method with polyvinyl alcohol as the emulsifier in the external aqueous phase was employed to prepare nanoparticles. The effects of monomethoxypoly(ethyleneglycol) (mPEG) segments in the polymer on particle size, zeta potential, encapsulation efficiency and in vitro release were investigated. It was found that the introduction of a certain amount of hydrophilic mPEG segments in the copolymer chains could improve the affinity of copolymer with plasmid DNA and enhance the emulsification ability of the copolymer. Thus DNA loaded nanoparticles with smaller particle sizes and higher encapsulation efficiencies were obtained by using PELGE copolymer as the matrix.     

Hydrovapothermal conversion of tetraethoxysilane vapor to polycrystalline zeolite layer by in situ gelation

Zeolite membrane has been fabricated on porous alumina substrate in a single continuous process of gelation and subsequent crystallization while suppressing nucleation of zeolite powder in the bulk.     

Progress of 3-aminopyridine-based amide,urea, imine and azo derivatives in supramolecular gelation

Supramolecular gels derived from low molecular weight gelators are considered to be fascinating soft and smart materials. Gelators of this class form gel networks involving noncovalent interactions and show various applications in many areas. The structural softness and the arrangement of the gelator molecules in the aggregated state have the collaborative effect to intensify the properties of the molecules for their potential applications in material chemistry. Of the various properties, stimulus responsibility is a desired property of supramolecular gel that finds profound application in sensing. In this review, a comprehensive summary of the work on 3-aminopyridine-based amide, urea, imine and azo gelators of different architectures indicating their different uses in supramolecular chemistry has been focused.     

Novel silver-containing supramolecular frameworks constructed by combination of coordination bonds and supramolecular interactions

The hydrothermal reactions of AgNO(3), 4,4'-bipy, and carboxylate ligands gave rise to three supramolecular architectures, namely [Ag(bipy)].H(2)SIPA.1/2bipy.H(2)O (1), [Ag(bipy)].1/2H(2)btec.H(2)O (2), and [Ag(bipy)](2).H(2)dpstc.2H(2)O (3) (H(3)SIPA = 5-sulfoisophthalic acid, bipy = 4,4'-bipyridine, H(4)btec = 1,2,4,5-benzenetetracarboxylic acid, H(4)dpstc = 3,3',4,4'-tetracarboxydiphenyl sulfone). All complexes are extended from Ag-bipy linear chains by the combination of coordination bonds and supramolecular interactions in two different approaches. Complexes 1 and 3 comprise two-dimensional frameworks. In the two complexes, a one-dimensional ladderlike structure is first formed by the connection of a Ag-bipy chain through hydrogen bonding between a free carboxylate/bipy ligand and weak coordinative interactions between a free carboxylate ligand and silver ion. The ladderlike structure is then extended to a two-dimensional layer architecture by pi...pi interactions between bipy ligands of the Ag-bipy chains. Complex 2 possesses a three-dimensional framework. The free H(2)btec(2)(-) ligands form a two-dimensional layer network by hydrogen-bonding interactions between protonated and deprotonated carboxylate groups; meanwhile, pi.pi interactions between bipy ligands of Ag-bipy chains also result in a two-dimensional layer. The two layers are further connected by weak Ag-O interactions to generate a three-dimensional supramolecular structure.     

In situ small-angle neutron scattering and rheological measurements of shear-induced gelation

The microscopic structure of shear-induced gels for a mixed solution of 2-hydroxyethyl cellulose and nanometer-size spherical droplets has been investigated by in situ small-angle neutron scattering (SANS) with a Couette geometry as a function of shear rate gamma. With increasing gamma, the viscosity increased rapidly at gamma approximately 4.0 s(-1), followed by a shear thinning. After cessation of shear, the system exhibited an extraordinarily large steady viscosity. This phenomenon was observed as a shear-induced sol-gel transition. Real-time SANS measurements showed an increase in the scattering intensity exclusively at low scattering angle region. However, neither orientation of polymer chains nor droplet deformation was detected and the SANS patterns remained isotropic irrespective of gamma. It took about a few days for the gel to recover its original sol state. A possible mechanism of gelation is proposed from the viewpoint of shear-induced percolation transition.     

Quantitation of plasmid DNA deposited on gold particles for particle-mediated epidermal delivery using ICP-MS

DNA-plasmid-based vaccines are a promising class of next generation therapeutics. Particle-mediated epidermal delivery is an attractive method for the administration of DNA plasmid vaccines. This technology utilizes minute quantities of DNA plasmid which have been deposited onto the surface of 2–3-μm gold particles, and so the development of this technology requires the use of analytical methods that can accurately quantitate the amount of the DNA on the particle. Spectroscopic methods are generally insufficient for this task due to interference from the gold particle. ICP-MS circumvents this issue while allowing for the sensitive, reproducible, and accurate determination of the quantity of DNA on the particle surface. This report will detail the development and application of such a method.     

Cyclodextrin/polyethylenimine-based supramolecular nanoparticles for loading and sustained release of ATP

A new supramolecular nanoparticle PEI/SCD was successfully constructed, showing the loading/sustained release abilities towards ATP.     

Lanthanide-doped chitosan nanospheres as cell nuclei illuminator and fluorescent nonviral vector for plasmid DNA delivery

Lanthanide-doped chitosan nanospheres (LDCNs) and lanthanide-Fe(3)O(4)-doped chitosan nanospheres (Fe(3)O(4)-LDCNs) are fabricated and show fluorescence, MRI effectiveness and desirable biocompatibility. Superior to most nanoparticles that were found retained in cytoplasmic organelles rather than the nucleus, the prepared chitosan nanospheres preferentially enter and illuminate the cell nuclei. Complexation of plasmid DNA (pDNA) to the nanospheres was accomplished via electrostatic forces between positively charged chitosan and negatively charged pDNA. Satisfactory results of the complexation indicate that the prepared chitosan nanospheres can serve as a potential fluorescent nonviral vector for pDNA delivery that can fulfill gene delivery and transfer efficiency assessment simultaneously, without an additional step of tagging fluorophores to the vectors carried out in fabrications of currently available pDNA delivery vectors.     

Targeted and sustained delivery of aclarubicin to lymphatics by lactic acid-oligomer microsphere in rat

We examined targeted delivery of an anticancer drug, aclarubicin (ACR), to the lymphatic system in rats by encapsulation of the drug in microsphere (MS) prepared from nontoxic and biodegradable L-lactic acid-oligomer with an average molecular weight (Mw) of 3600. ACR was released at an almost constant rate from two kinds of ACR-MSs having different size (1-5 microns and less than 1 micron) over 20 d in phosphate-buffered saline at 37 degrees C. The intraperitoneal administration of both ACR-MSs (dose of ACR; 5 mg/kg) to rats sustained an almost constant ACR level (300-400 and 400-600 ng/ml) in the lymph of the thoracic duct during over 10 d, and the ACR level in the blood was extremely low, although intraperitoneal injection of ACR alone gave lower level of ACR in the lymph than in the blood level within 12 h.     

Ozonolysis-based route to the in situ formation of aldehyde-bearing self-assembled monolayer surfaces

While ozonolysis of a terminal carbon-carbon double bond to produce aldehydes is a well-established synthetic strategy for conventional solution chemistry, exposure of vinyl-terminated self-assembled monolayers to ozone has been reported to yield carboxylic acids. By using a cold solution of ozone in methanol and then adding a reducing agent to this solution, acid formation is minimized and near-quantitative aldehyde formation is achieved. The aldehyde-bearing surface is characterized by its physical and chemical properties and by ATR-FTIR spectroscopy showing a characteristic aldehyde C-H peak at 2715 cm(-1) and carbonyl peak at 1729 cm(-1). The reactivity of the aldehyde-bearing surface is shown by its reaction with amines and amine derivatives to give surface-bound imines and by the reversible cycling between aldehyde and acetal. The acetal also provides a useful way to mask the aldehyde and store readily released aldehyde surface functionality for subsequent surface elaboration.     

Novel route to the synthesis of 4-quinolyl isothiocyanates

4-Quinolyl isothiocyanates were synthesized in a regiospecific fashion from the corresponding 4-chloroquinolines and silver thiocyanate in refluxing toluene. The products were isolated in quantitative yield and high purity (>95%) by simple filtration and concentration. Reactivity and mechanism of the reaction are discussed. The new approach would provide a new mean which had been lacking for the synthesis of functionalized 4-quinolinyl isothiocyanate.     

Recent advances in biocompatible supramolecular assemblies for biomolecular detection and delivery

Inspired by sophisticated biological structures and their physiological processes,supramolecular chemistry has been developed for understanding and mimicking the behaviors of natural species. Through spontaneous self-assembly of functional building blocks,we are able to control the structures and regulate the functions of resulting supramolecular assemblies.Up to now,numerous functional supramolecular assemblies have been constructed and successfully employed as molecular devices, machines and biological diagnostic platforms.This review will focus on molecular structures of functional molecular building blocks and their assembled superstructures for biological detection and delivery.     

Novel route to dendritic structures and their application for surface modification

Monodisperse branched polyurethanes containing long alkyl chains have been prepared by a new convergent synthesis. This synthesis comprises two steps, with hexamethylene diisocyanate uretdione as the starting molecule. The free isocyanate groups of this monomer are reacted with long‐chain alkanols. These diurethane uretdiones are then reacted with amines or amino alcohols under ring opening and the formation of a biuret group. Branching points are not, as usual, part of the monomer but are formed during preparation. The structure of these dendrons has been established with NMR spectroscopy, elemental analysis, mass spectroscopy, and gel permeation chromatography. The dendritic polyurethanes are thermally stable up to 200 °C. Surfaces coated with these materials are hydrophobic. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 1372–1386, 2006     

Spatiotemporal dynamics of supramolecular polymers by in situ quantitative catalyst-free hydroamination

Implementing chemical reactivity into synthetic supramolecular polymers based on π-conjugated molecules has been of great interest to create functional materials with spatiotemporal dynamic properties. However, the development of an in situ chemical reaction within supramolecular polymers is still in its infancy, because one needs to design optimal π-conjugated monomers having excellent reactivity under mild conditions possibly without byproducts or a catalyst. Herein we report the synthesis of a supramolecular polymer based on ethynyl core-substituted naphthalenediimide (S-NDI2) molecules that react with various amines quantitatively in a nonpolar solvent, without a catalyst, at 298 K. Most interestingly, the in situ reaction of the S-NDI2 supramolecular polymer with a linear aliphatic diamine proceeded much faster than the homogeneous reaction of a monomeric naphthalenediimide with the same diamine, affording diamine-linked S-NDI2 oligomers and polymers. The acceleration of in situ hydroamination was presumably due to rapid intra-supramolecular cross-linking between ethynyl and amino groups fixed in close proximity within the supramolecular polymer. Such intra-supramolecular cross-linking did not occur efficiently with an incompatible diamine. The systematic kinetic studies of in situ catalyst-free hydroamination within supramolecular polymers provide us with a useful, facile and versatile tool kit for designing dynamic supramolecular polymeric materials based on electron-deficient π-conjugated monomers.

A supramolecular polymer based on ethynyl core-substituted naphthalenediimides reacted with various amines quantitatively without a catalyst, exhibiting unconventional reaction kinetics and products.     

Fabrication of supramolecular hydrogels for drug delivery and stem cell encapsulation

Supramolecular hydrogels self-assembled by alpha-cyclodextrin and methoxypolyethylene glycol-poly(caprolactone)-(dodecanedioic acid)-poly(caprolactone)-methoxypolyethylene glycol (MPEG-PCL-MPEG) triblock polymers were prepared and characterized in vitro and in vivo. The sustained release of dextran-fluorescein isothiocyanate (FITC) from the hydrogels lasted for more than 1 month, which indicated that the hydrogels were promising for controlled drug delivery. ECV304 cells and marrow mesenchymal stem cells (MSC) were encapsulated and cultured in the hydrogels, during which the morphologies of the cells could be kept. The in vitro cell viability studies and the in vivo histological studies demonstrated that the hydrogels were non-cytotoxic and biocompatible, which indicated that the hydrogels prepared were promising candidates as injectable scaffolds for tissue engineering applications.