Radiation formation of polymeric nanogels

An alternative method of synthesis of polymeric nanogels is proposed, based not on polymerization, but on intramolecular crosslinking of polymer chains, initiated by pulse irradiation in dilute aqueous solutions. Kinetic data show that for many water-soluble polymers irradiation under these conditions result in intramolecular crosslinking. Preliminary product studies on poly(vinyl alcohol) indicate that in fact internally crosslinked macromolecules can be obtained by this technique.     

Characterizing property distributions of polymeric nanogels by size-exclusion chromatography

Nanogels are highly branched, swellable polymer structures with average diameters between 1 and 100nm. Size-exclusion chromatography (SEC) fractionates materials in this size range, and it is commonly used to measure nanogel molar mass distributions. For many nanogel applications, it may be more important to calculate the particle size distribution from the SEC data than it is to calculate the molar mass distribution. Other useful nanogel property distributions include particle shape, area, and volume, as well as polymer volume fraction per particle. All can be obtained from multi-detector SEC data with proper calibration and data analysis methods. This work develops the basic equations for calculating several of these differential and cumulative property distributions and applies them to SEC data from the analysis of polymeric nanogels. The methods are analogous to those used to calculate the more familiar SEC molar mass distributions. Calibration methods and characteristics of the distributions are discussed, and the effects of detector noise and mismatched concentration and molar mass sensitive detector signals are examined.     

Core–shell nanogels by RAFT crosslinking polymerization: Synthesis and characterization

A synthetic methodology is described for the preparation of core–shell nanogels by reversible addition‐fragmentation chain transfer. Well‐defined macro chain transfer agents (macro‐CTA's) were prepared in a first step using monomers that yield sensitive polymers. In the second step, a crosslinker alone or with the addition of a functionalized comonomer were used to form a crosslinked core. The ratio of crosslinker to macro‐CTA is crucial to yield nanogels. Furthermore, the polymerization time has an impact in the architecture of the nanomaterial obtained: it evolves from a core‐crosslinked star to a core–shell nanogel. Controlling the molecular weight of the macro‐CTA and the type of comonomer in the core forming step, core–shell nanogels with hydrodynamic diameters from 22 to 168 nm and a core that represents from 35 to 77% of the size, were prepared containing functional groups in the core which could be used as catalytic scaffolds. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012.     

Recent progress of polymeric nanogels for gene delivery

With its nearly unrestricted possibilities, gene therapy attracts more and more significance in modern-day research. The only issue still seeming to hold back its clinical success is the actual effective delivery of genetic material. Nucleic acids are in general challenging to administer to their intracellular targets because of their unfavorable pharmaceutical characteristics. Polymeric nanogels present a promising delivery platform for oligonucleotide-based therapies, as the growing number of reports deliberated in this review represents. Within the scope of this article, recent progress in the use of nanogels as gene delivery vectors is summarized and different examples of modified, stimuli-responsive, targeted, and codelivering nanogels are discussed in detail. Furthermore, major aspects of successful gene delivery are addressed and critically debated in regard to nanogels, giving insights into what progress has been made and which key issues still need to be further approached.     

Luminescent amphiphilic nanogels by terpyridine-Zn(II) complexation of polymeric micelles

In this work, we investigated terpyridine (tpy)/Zn(II) complexation for the crosslinking of polymeric micelles of the branched poly(ethylene oxide)–poly(propylene oxide) block copolymer Tetronic® 1107 (T1107) in water and produce physically stable amphiphilic luminescent nanogels. Nanoparticles displayed a size of 235 ± 25 and 318 ± 57 nm before and after Zn(II) crosslinking, respectively, as measured by dynamic light scattering. High-resolution scanning electron microscopy analysis revealed the multimicellar nature of the crosslinked nanoparticles. In addition, Zn(II) complexation prevented nanoparticle disassembly after extreme dilution below the critical micellar concentration and reduced the minimum concentration required for the reverse thermal gelation of concentrated aqueous T1107 systems. The cell compatibility and uptake were initially assessed in the murine macrophage cell line RAW 264.7. Results showed that complexation increases the cell compatibility of the nanoparticles with respect to the non-complexed counterparts. In addition, non-crosslinked nanoparticles accumulated in the cell membrane, while the complexed ones were internalized, as observed by confocal laser scanning fluorescence microscopy. Then, the antiproliferative activity of the crosslinked nanoparticles was confirmed in the rhabdomyosarcoma cell line Rh30; their inhibitory concentration 50 (IC₅₀) being 101 μg/mL (6.7 μM). Finally, the encapsulation and release of the hydrophobic antiretroviral efavirenz was characterized in vitro. Complexation slightly reduced the release kinetics with respect to the pristine nanoparticles. Overall results demonstrate the promise of this simple modification strategy to produce amphiphilic nanogels with a set of advantageous physicochemical, optical, and biological properties.     

Spherical hydrophilic microparticles obtained by the radical copolymerisation of functionalised bovine serum albumin

Unsaturated groups were introduced onto proteins in order to produce macromers that are able to undergo radical polymerisation. The initial protein used was bovine serum albumin (BSA) because it is biodegradable, biocompatible and easily available. Methacrylic groups were introduced onto BSA by reaction with methacrylic anhydride at controlled pH and temperature. The experimental conditions allowed the protein to be kept water-soluble. This water-solubility of the derivatised protein was essential when realising spherical polymeric microparticles via reverse phase suspension copolymerisation with N,N-dimethyacrylamide (DMAA). During the derivatisation, the insertion of the polymerisable groups affects only the sterically-available chemical functions of the native protein. Therefore, chain growth during the copolymerisation process involves only these groups, achieving a polymeric network around a structurally unmodified protein. The polymeric systems show high water affinity, ascribable to the hydrophilic properties of BSA. We have demonstrated that the achievement of the spherical form during the polymerisation depends on two factors: the degree of derivatisation of BSA, and the weight/weight (w/w) ratio of the protein to the comonomer. The beads obtained were characterised by Fourier transform IR spectrophotometry, particle size distribution analysis, and scanning electron microscopy (SEM). The samples investigated showed a remarkable affinity for water and a high swelling capacity. These properties depend upon the degree of derivatisation of BSA and on the percentage of DMAA in the copolymerisation mixture. In this paper we describe the starting materials and the experimental conditions used to prepare protein hydrogels by radical copolymerisation, which are intended for use in pharmaceutical and biomedical applications.     

Regioselective alkylation of 3,4-dihydro-2H-pyran by xanthate-mediated free radical nonchain process

An intermolecular xanthate-mediated free radical nonchain addition reaction is introduced for the regioselective alkylation of 3,4-dihydro-2H-pyran. Additionally, we observed that the free radical nonchain reaction depends on the nature of the radical precursor.     

Fluorous-phase soluble polymeric supports

Fluorous phase soluble polymer supports derived from fluoroacrylate polymers are described. N-Acryloxysuccinimide-containing fluoroacrylate polymers were readily prepared from commercially available monomers. The activated acrylates so prepared were then converted into chelating and non-chelating ligands by amidation of the N-acryloxysuccinimide active ester residues. Phosphine ligands attached to these supports were used to prepare neutral and cationic rhodium(I) hydrogenation catalysts as well as palladium(0) catalysts. Similar substitution of pendant active ester groups to form hydroxamic acid ligands for metal sequestration is also feasible. Liquid/liquid extraction readily separated, recycled and reused these polymer-bound ligands and catalysts. While fluorous phase solubility could be attained with polymers containing only heptafluorobutyryl groups, selective solubility in a fluorous phase in contact with an organic phase was only seen with fluoroacrylates that contained larger fluorinated ester groups.     

Polymer-protein conjugates from omega-aldehyde endfunctional poly(N-vinylpyrrolidone) synthesised via xanthate-mediated living radical polymerisation

Aldehyde omega-endfunctional poly(N-vinylpyrrolidone) was synthesised via quantitative conversion of a xanthate endfunctional precursor obtained via RAFT-mediated polymerisation.     

Biohybrid nanogels by crosslinking of ovalbumin with reactive star‐PEGs in W/O emulsions

This article reports the synthesis of biohybrid nanogels by crosslinking six‐arm acrylate functionalized star shaped P(EO‐stat‐PO) with the amine groups of various amino acids of a hen egg ovalbumin in W/O emulsion. PEG Poly(ethylene glycol)‐diamines of different molecular weights (368.5 g/mol, 897.1 g/mol, 3000 g/mol, and 6000 g/mol) were used to optimize the crosslinking reactions in aqueous droplets. The increase of molecular weight of the PEG‐diamine led to decrease of the nanogel size due to better stabilization by longer PEG chains. The size of the ovalbumin nanogels was independent of the acrylate‐sP(EO‐stat‐PO):ovalbumin ratio in the reaction mixture. The bicinchoninic acid (BCA) assay proved that the ovalbumin has been effectively crosslinked by reactive prepolymers. From the results of BCA assay, it can also be established that there exists a limiting amount of ovalbumin which can be incorporated into the nanogels. Both Diamine and ovalbumin‐based nanogels exhibit amphoteric behavior and display a positive charge in acidic and a negative charge in basic environment. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Total synthesis of 10-norparvulenone and of O-methylasparvenone using a xanthate-mediated free radical addition-cyclization sequence

[reaction: see text] A short synthesis of (+/-)-10-norparvulenone and (+/-)-O-methylasparvenone was developed starting from commercially available m-methoxyphenol, hinging on a xanthate-mediated addition-cyclization sequence for the construction of the alpha-tetralone subunit.     

Novel nanogels as drug delivery systems for poorly soluble anticancer drugs

Two types of novel nanogels were prepared using shell cross-linking of Pluronic F127 micelles with polyethylenimine (PEI) (F127/PEI nanogel), and penetrating network of poly(butylcyanoacrylate) (PBCA) in Pluronic F127 micelles (F127/PBCA nanogel). Poorly soluble anticancer drug, paclitaxel (PTX) and 10-hydroxycamptothecin (HCPT), were used as model drugs and incorporated into nanogels. The results obtained from FT-IR spectroscopy confirmed that the drugs were molecularly dispersed in the nanogels. DLS measurements demonstrated that the nanogel size distribution was narrow with average diameter less than 200 nm. TEM images indicated that the nanogels were spherical in shape and had smooth surfaces. The drug-loaded nanogels showed sustained release profiles compared with the free drugs as revealed by in vitro release experiments. Cytotoxicity tests showed that the cytotoxicity of drug-loaded nanogels against cancer cell in vitro was much higher than that of the free drug. The data demonstrate that these novel nanogels improved stability towards dilution, increased solubility and showed better cellular uptake by cells compared with free drug.     

Oxidative cyclorelease from soluble polymeric supports

[reaction: see text] Single electron oxidation is shown to be a viable method for effecting concomitant cyclization and cleavage (cyclorelease) of a series of polymer bound homobenzylic ethers. Soluble oligonorbornene polymers are stable toward redox chemistry and are isolable through precipitation with methanol, making them excellent supports for this process. These oxidative conditions are also shown to cleave secondary and tertiary alcohols and ethers in a new traceless approach to polymer-supported aldehyde and ketone synthesis.     

Concurrent binding and delivery of proteins and lipophilic small molecules using polymeric nanogels

Supramolecular nanoassemblies, which are capable of binding and delivering either lipophilic small molecules or hydrophilic molecules, are of great interest. Concurrently binding and delivering this combination of molecules is cumbersome, because of the opposing supramolecular host requirements. We describe the development of a versatile nanoassembly system that is capable of binding and delivering both, a protein and a lipophilic small molecule, simultaneously inside the cells.     

Preparation of polymeric alcohol bearing oligo(oxyethylene) moiety by radical polyaddition through ketyl radical

Hydrophilic polymers having both oligo(oxyethylene) moieties and tertiary alcohol units in the main chain were prepared by the radical polyaddition of the dike-tones with distyryl compounds by using samarium(II) iodide as an electron transfer agent. Polyaddition of 4,4′-(1,4-phenylene)bis-2-butanone or 6,9-dioxatetradeca-2,13-dione with distyryl compounds such as 1,15-di(4-ethenylphenyl)-2,5,8,11,14-pentaoxapentadecane, 1,18-di(4-ethenylphenyl)-2,5,8,11,14,17-hexaoxaoctadecane, or 1,21-di(4-ethenylphenyl)-2,5,8,11,14,17,20-heptaoxaheneicosane resulted in the formation of the corresponding polymeric alcohols in moderate yields (46–75%). The produced polymers showed high solubility in common solvents, and their molecular weights estimated by GPC (THF, polystyrene standard) were 5200–8100. No serious difference in the molecular weight of the polymer between after and before the treatment with cerium ammonium nitrate indicated that the produced polymers were inert under the oxidative condition where oxidative cleavage of the main chain of poly(vinyl alcohol) takes place. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35: 715–720, 1997     

Photoinitiated radical chains in solid polymeric methacrylates

Polymeric methacrylates functionalized with free methacryloyl groups are efficiently crosslinked in the presence of transition-metal carbonyls on UV irradiation of the polymeric solid. The reaction proceeds by a radical chain mechanism with a kinetic chain length of about 10 in a solvent-free polymer containing 10^?3 mole of methacryloyl groups per cm³. The chain length increases steeply when the glass transition of the polymer is reached, either by plastification or by an increase in temperature. The temperature dependence of the crosslinking yield below the glass transition is consistent with an activation energy of about 9 kcal mole^?1. The addition of acrylic monomers enhances chain propagation by up to an order of magnitude. Postirradiative crosslinking in the matrix comes to a standstill well before all acrylic groups or radicals have been exhausted: if, after cessation of the primary reaction, the matrix is briefly heated, a second crop of crosslinks is obtained without further exposure. The system behaves thus as if the radicals had been removed into traps from which they can be set free by thermal activation. From an analysis of the reaction kinetics it appears that in the glassy polymer 90% of the radicals are inactivated in this way. Radical recombination, however, is the principal mechanism of chain termination above the glass transition. From the kinetic data, diffusion coefficients for polymer-bound groups are found to be in the range of 10^?17–10^?16 cm² sec^?1 in the glassy polymer at room temperature. They are of the order of 10^?14 cm² sec^?1 in plasticized films above the glass transition.     

Asymmetric aldol reactions on a soluble polymeric support

[reaction: see text] The combinatorial synthesis of small, nonpeptidic compounds is of increasing interest in current medicinal chemistry. To meet this demand, efficient entries, preferentially on polymeric supports, to pharmacologically interesting classes of compounds such as polyketides are necessary. Therefore, we have developed a synthetic protocol allowing for the asymmetric synthesis of diketides on the soluble support MeOPEG-5000. The strategy employed mainly allows for repeated aldolizations, thus providing access to functionalized polyketides of varying degree of oligomerization.     

Synthesis of soluble oligo- and polymeric pentacene-based materials

Functionalization of pentacene at the 6- and 13-positions affords versatile building blocks for oligomer and polymer formation. Di- and trimeric materials are synthesized using unsymmetrical building block 18, while symmetrical diol monomer 17 allows for the synthesis of polymers. The materials reported herein are soluble in common organic solvents and air-stable. UV-vis and fluorescence spectroscopic properties have been investigated. Solid-state X-ray crystallography of building blocks 17 and 19 shows that these derivatives can π-stack with significant acene face-to-face interactions with spacing of less than 3.5 Å.     

Preparation of thermosensitive nanogels by photo-cross-linking

 A novel method to prepare thermosensitive nanogels from photocross-linkable copolymers of N-isopropylacrylamide and dimethyl maleinimido acrylamide (DMIAAm) was developed. The colloidal nanogels were formed by UV irradiation of solutions of thermosensitive polymers in water at 45 °C. The compositions of the photopolymer solutions were varied by changing the amount of DMIAAm in the photopolymer chains (2–10 mol%) or by varying the sodium dodecyl sulfate (SDS) concentration. The resultant nanogel particles were rather spherical and showed large changes in hydrodynamic diameters in the vicinity of the phase transition temperature of the corresponding linear photopolymers. The particle sizes of the nanogels and their swellability could be controlled through the UV irradiation time, the chromophore content and the SDS concentration. An increase in the chromophore content and the SDS concentration resulted in nanogels with smaller dimensions. The hydrodynamic diameters of the nanogels decreased significantly from 2 to 10 min UV irradiation time but not significantly after that. The phase transition of the photopolymer solutions and the respective nanogels could be adjusted by the chromophore content or the SDS concentration. An increase in the chromophore content leads to lower phase-transition temperatures, whilst an increase in the SDS concentration elevated them. Pulsed-field-gradient NMR proved a useful tool to investigate the network formation in the nanogels by determining changes in the diffusion coefficients. Received: 14 May 2001 Accepted: 1 June 2001