Polyvalent Diazonium Polymers Provide Efficient Protection of Oncolytic Adenovirus Enadenotucirev from Neutralizing Antibodies while Maintaining Biological Activity In Vitro and In Vivo.

Oncolytic viruses offer many advantages for cancer therapy when administered directly to confined solid tumors. However, the systemic delivery of these viruses is problematic because of the host immune response, undesired interactions with blood components, and inherent targeting to the liver. Efficacy of systemically administered viruses has been improved by masking viral surface proteins with polymeric materials resulting in modulation of viral pharmacokinetic profile and accumulation in tumors in vivo. Here we describe a new class of polyvalent reactive polymer based on poly( N-(2-hydroxypropyl)methacrylamide) (polyHPMA) with diazonium reactive groups and their application in the modification of the chimeric group B oncolytic virus enadenotucirev (EnAd). A series of six copolymers with different chain lengths and density of reactive groups was synthesized and used to coat EnAd. Polymer coating was found to be extremely efficient with concentrations as low as 1 mg/mL resulting in complete (>99%) ablation of neutralizing antibody binding. Coating efficiency was found to be dependent on both chain length and reactive group density. Coated viruses were found to have reduced transfection activity both in vitro and in vivo, with greater protection against neutralizing antibodies resulting in lower transgene production. However, in the presence of neutralizing antibodies, some in vivo transgene expression was maintained for coated virus compared to the uncoated control. The decrease in transgene expression was found not to be solely due to lower cellular uptake but due to reduced unpackaging of the virus within the cells and reduced replication, indicating that the polymer coating does not cause permanent inactivation of the virus. These data suggest that virus activity may be modulated by the appropriate design of coating polymers while retaining protection against neutralizing antibodies.

Alkyl-Modified Oligonucleotides as Intercalating Vehicles for Doxorubicin Uptake via Albumin Binding.

DNA-based drug delivery vehicles have displayed promise for the delivery of intercalating drugs. Here, we demonstrate that oligonucleotides modified with an alkyl chain can bind to human serum albumin, mimicking the natural binding of fatty acids. These alkyl-DNA-albumin complexes display excellent serum stability and are capable of strongly binding doxorubicin. Complexes are internalized by cells in vitro, trafficking to the mitochondria, and are capable of delivering doxorubicin with excellent efficiency resulting in cell death. However, the cellular localization of the delivered doxorubicin, and ultimately the complex efficacy, is dependent on the nature of the linker between the alkyl group and the oligonucleotide.

Control of aggregation temperatures in mixed and blended cytocompatible thermoresponsive block co-polymer nanoparticles.

A small library of thermoresponsive amphiphilic copolymers based on polylactide-block-poly((2-(2-methoxyethoxy)ethyl methacrylate)-co-(oligoethylene glycol methacrylate)) (PLA-b-P(DEGMA)-co-(OEGMA)), was synthesised by copper-mediated controlled radical polymerisation (CRP) with increasing ratios of OEGMA : DEGMA. These polymers were combined in two ways to form nanoparticles with controllable thermal transition temperatures as measured by particle aggregation. The first technique involved the blending of two (PLA-b-P(DEGMA)-co-(OEGMA)) polymers together prior to assembling nanoparticles (NPs). The second method involved mixing pre-formed nanoparticles of single (PLA-b-P(DEGMA)-co-(OEGMA)) polymers. The observed critical aggregation temperature Tt did not change in a linear relationship with the ratios of each copolymer either in the nanoparticles blended from different copolymers or in the mixtures of pre-formed nanoparticles. However, where co-polymer mixtures were based on (OEG)9MA ratios within 5-10 mole%, a linear relationship between (OEG)9MA composition in the blends and Tt was obtained. The data suggest that OEGMA-based copolymers are tunable over a wide temperature range given suitable co-monomer content in the linear polymers or nanoparticles. Moreover, the thermal transitions of the nanoparticles were reversible and repeatable, with the cloud point curves being essentially invariant across at least three heating and cooling cycles, and a selected nanoparticle formulation was found to be readily endocytosed in representative cancer cells and fibroblasts.

Influence of Polymer Size on Uptake and Cytotoxicity of Doxorubicin-Loaded DNA-PEG Conjugates.

Intercalation of drugs into assembled DNA systems offers versatile new mechanisms for controlled drug delivery. However, current systems are becoming increasingly complex, reducing the practicality of large scale production. Here, we demonstrate a more pragmatic approach where a short DNA sequence was modified with poly(ethylene glycol) (PEG) of various lengths at both 5'-termini to provide serum stability and compatibility. The anticancer drug doxorubicin was physically loaded into two designed binding sites on the dsODN. The polymer conjugation improved the stability of the dsODN toward serum nucleases while its doxorubicin binding affinity was unaffected by the presence of the polymers. We examined the effects of polymer size on the dsODN carrier characteristics and studied the resulting DOX@DNA-PEG systems with respect to cytotoxicity, cellular uptake, and localization in A549 and MCF7 cell lines. For the A549 cell line the DOX@DNA-PEG1900 exhibited the best dose response of the conjugates while DOX@DNA-PEG550 was the least potent. In MCF-7, a more doxorubicin sensitive cell line, all conjugates exhibited similar dose response to that of the free drug. Confocal microscopy analysis of doxorubicin localization shows that conjugates successfully deliver doxorubicin to the cell nucleus and also the lysosome. These data provide a valuable insight into the complexities of designing an oligonucleotide based drug delivery system and highlight some practical issues that need to be considered when doing so.

Bacteria-instructed synthesis of polymers for self-selective microbial binding and labelling.

The detection and inactivation of pathogenic strains of bacteria continues to be an important therapeutic goal. Hence, there is a need for materials that can bind selectively to specific microorganisms for diagnostic or anti-infective applications, but that can be formed from simple and inexpensive building blocks. Here, we exploit bacterial redox systems to induce a copper-mediated radical polymerization of synthetic monomers at cell surfaces, generating polymers in situ that bind strongly to the microorganisms that produced them. This 'bacteria-instructed synthesis' can be carried out with a variety of microbial strains, and we show that the polymers produced are self-selective binding agents for the 'instructing' cell types. We further expand on the bacterial redox chemistries to 'click' fluorescent reporters onto polymers directly at the surfaces of a range of clinical isolate strains, allowing rapid, facile and simultaneous binding and visualization of pathogens.

Phosphonium Polymethacrylates for Short Interfering RNA Delivery: Effect of Polymer and RNA Structural Parameters on Polyplex Assembly and Gene Knockdown.

Synthetic polymers containing quaternary phosphonium salts are an emerging class of materials for the delivery of oligo/polynucleotides. In this work, cationic phosphonium salt-containing polymethacrylates and their corresponding ammonium analogues were synthesized by reversible addition-fragmentation chain transfer polymerization. Both the nature of the charged heteroatom (N vs P) and the length of the spacer separating the cationic units along the polymer backbone (oxyethylene vs trioxyethylene) were systematically varied. Polymers efficiently bound short interfering RNA (siRNA) at N(+)/P(-) or P(+)/P(-) ratios of 2 and above. At a 20:1 ratio, small polyplexes (Rh: 4-15 nm) suitable for cellular uptake were formed that displayed low cytotoxicity. While siRNA polyplexes from both ammonium and phosphonium polymers were efficiently internalized by green fluorescent protein (GFP)-expressing 3T3 cells, no knockdown of GFP expression was observed. However, 65% Survivin gene knockdown was observed when siRNA was replaced with novel, multimerized long interfering RNA in HeLa cells, demonstrating the importance of RNA macromolecular architecture on RNA-mediated gene silencing.

Electrospinning polymersomes into bead-on-string polyethylene oxide fibres for the delivery of biopharmaceuticals to mucosal epithelia.

Fibrous mucoadhesive polymer membranes prepared using electrospinning demonstrate many advantages for mucosal drug delivery compared to other formulations. Previous electrospun membrane formulations have been developed mainly for the delivery of small molecule drugs. There remains great potential to further develop the technology for the delivery of vesicular vectors that allow administration of advanced therapeutic agents. However, there are no previous reports demonstrating the release of intact drug delivery vesicles from electrospun materials. Here, we describe incorporation and release of protein-loaded polymersomes from polyethylene oxide (PEO)-based electrospun membranes. Polymersomes comprising a copolymer of glycerol monomethacrylate (GMA) and hydroxypropyl methacrylate (HPMA) were prepared using polymerization-induced self-assembly and incorporated within PEO membranes using bead-on-string electrospinning at approximately 40 % w/w by polymer mass. Super-resolution fluorescence imaging showed that the vesicles remained intact and retained their encapsulated protein load within the fibre beads. Transmission electron microscopy and dynamic light scattering demonstrated that polymersomes retained their morphology following release from the polymer fibres. F(ab) antibody fragments were encapsulated within polymersomes and then electrospun into membranes. 78 ± 13 % of the F(ab) remained encapsulated within polymersomes during electrospinning and retained functionality when released from electrospun membranes, demonstrating that the formulation is suitable for the delivery of biologics. Membranes were non-irritant to the oral epithelium and fluorescence microscopy detected accumulation of polymersomes within the epithelia following application. This innovative drug delivery approach represents a novel and potentially highly useful method for the administration of large molecular mass therapeutic molecules to diseased mucosal sites.

Bioactive Protein and Peptide Release from a Mucoadhesive Electrospun Membrane.

Protein-based biologics constitute a rapidly expanding category of therapeutic agents with high target specificity. Their clinical use has dramatically increased in recent years, but administration is largely via injection. Drug delivery across the oral mucosa is a promising alternative to injections, in order to avoid the gastrointestinal tract and first-pass metabolism. Current drug delivery formulations include liquid sprays, mucoadhesive tablets and films, which lack dose control in the presence of salivary flow. To address this, electrospun membranes that adhere tightly to the oral mucosa and release drugs locally have been developed. Here, we investigated the suitability of these mucoadhesive membranes for peptide or protein release. Bradykinin (0.1%) or insulin (1, 3, and 5%) were incorporated by electrospinning from ethanol/water mixtures. Immersion of membranes in buffer resulted in the rapid release of bradykinin, with a maximal release of 70 ± 12% reached after 1 h. In contrast, insulin was liberated more slowly, with 88 ± 11, 69.0 ± 5.4, and 63.9 ± 9.0% cumulative release of the total encapsulated dose after 8 h for membranes containing 1, 3, and 5% w/w insulin, respectively. Membrane-eluted bradykinin retained pharmacological activity by inducing rapid intracellular calcium release upon binding to its cell surface receptor on oral fibroblasts, when examined by flow cytometry. To quantify further, time-lapse confocal microscopy revealed that membrane-eluted bradykinin caused a 1.58 ± 0.16 fold-change in intracellular calcium fluorescence after 10 s compared to bradykinin solution (2.13 ± 0.21), relative to placebo. In conclusion, these data show that electrospun membranes may be highly effective vehicles for site-specific administration of biotherapeutic proteins or peptides directly to the oral mucosa for either local or systemic drug delivery applications.

Multi-modal switching in responsive DNA block co-polymer conjugates.

New classes of information-rich DNA block co-polymer conjugates were synthesised, encoded with thermoresponsive and biocompatible poly(tri(ethylene glycol)ethyl ether methacrylate) (pTriEGMA) chains and oligomeric nucleic acids connected by either bioreducible or non-reducible links. The pTriEGMA chains were grown from initiator-functionalised hybridised DNA, designed to assemble with toehold overhangs. Functional information in the conjugates was explored via dynamic light scattering (DLS) and atomic force microscopy (AFM), in order to evaluate (i) reversible self-assembly into supramolecular structures across the pTriEGMA phase transition temperature; (ii) conformational change via addition of competing DNA sequences across the toeholds, and (iii) reductive cleavage of polymer-DNA links. The results showed that discrete nanoscale conjugates could reversibly associate through pTriEGMA phase behaviour and that size and association behaviour in one class of conjugate could be switched by addition of a competing DNA sequence and by reduction to break the polymer-DNA links. Preliminary experiments with the DNA-conjugates as delivery systems for doxorubicin to a cancer cell line indicated good tolerability of the conjugates alone and cytotoxic efficacy when loaded with the drug.

Synthesis of 5-Fluorouracil Polymer Conjugate and 19F NMR Analysis of Drug Release for MRI Monitoring.

To monitor the release of fluorinated drugs from polymeric carriers, a novel 19F MRI enzyme-responsive contrast agent was developed and tested. This contrast agent was prepared by conjugation of 5-fluorouracil (5-FU) to hyperbranched poly(N,N-dimethylacrylamide) (HB-PDMA) via an enzyme-degradable peptide linker. Due to the different molecular sizes, the release of 5-FU from the 5-FU polymer conjugate resulted in a sufficiently substantial difference in spin-spin T219F NMR/MRI relaxation time that enabled differentiating between attached and released drug states. The 5-FU polymer conjugate exhibited a broad signal and short T2 relaxation time under 19F NMR analysis. Incubation with the enzyme induced the release of 5-FU, accompanied by an extension of T2 relaxation times and an enhancement in the 19F MRI signal. This approach is promising for application in the convenient monitoring of 5-FU drug release and can be used to monitor the release of other fluorinated drugs.

Electrospun patch delivery of anti-TNFα F(ab) for the treatment of inflammatory oral mucosal disease.

Chronic ulcerative oral mucosal inflammatory diseases, including oral lichen planus and recurrent aphthous stomatitis, are painful and highly prevalent, yet lack effective clinical management. In recent years, systemic biologic therapies, including monoclonal antibodies that block the activity of cytokines, have been increasingly used to treat a range of immune-mediated inflammatory conditions such as rheumatoid arthritis and psoriasis. The ability to deliver similar therapeutic agents locally to the oral epithelium could radically alter treatment options for oral mucosal inflammatory diseases, where pro-inflammatory cytokines, in particular tumour-necrosis factor-α (TNFα), are major drivers of pathogenesis. To address this, an electrospun dual-layer mucoadhesive patch comprising medical-grade polymers was investigated for the delivery of F(ab) biologics to the oral mucosa. A fluorescent-labelled F(ab) was incorporated into mucoadhesive membranes using electrospinning with 97% v/v ethanol as a solvent. The F(ab) was detected within the fibres in aggregates when visualised by confocal microscopy. Biotinylated F(ab) was rapidly eluted from the patch (97 ± 5% released within 3 h) without loss of antigen-binding activity. Patches applied to oral epithelium models successfully delivered the F(ab), with fluorescent F(ab) observed within the tissue and 5.1 ± 1.5% cumulative transepithelial permeation reached after 9 h. Neutralising anti-TNFα F(ab) fragments were generated from whole IgG by papain cleavage, as confirmed by SDS-PAGE, then incorporated into patches. F(ab)-containing patches had TNFα neutralising activity, as shown by the suppression of TNFα-mediated CXCL8 release from oral keratinocytes cultured as monolayers. Patches were applied to lipopolysaccharide-stimulated immune-competent oral mucosal ulcer equivalents that contained primary macrophages. Anti-TNFα patch treatment led to reduced levels of active TNFα along with a reduction in the levels of disease-implicated T-cell chemokines (CCL3, CCL5, and CXCL10) to baseline concentrations. This is the first report of an effective device for the delivery of antibody-based biologics to the oral mucosa, enabling the future development of new therapeutic strategies to treat painful conditions.

Solution and Solid-State Behavior of Amphiphilic ABA Triblock Copolymers of Poly(acrylic acid-stat-styrene)-block-poly(butyl acrylate)-block-poly(acrylic acid-stat-styrene).

A combination of statistical and triblock copolymer properties is explored to produce stable aqueous polymer dispersions suitable for the film formation. In order to perform an extensive structural characterization of the products in the dissolved, dispersed, and solid states, a wide range of symmetrical poly(acrylic acid-stat-styrene) x -block-poly(butyl acrylate) y -block-poly(acrylic acid-stat-styrene) x , poly(AA-st-St) x -b-PBA y -b-poly(AA-st-St) x , (x = 56, 108 and 140, y = 100-750; the AA:St molar ratio is 42:58) triblock copolymers were synthesized by reversible addition-fragmentation chain transfer (RAFT) solution polymerization using a bifunctional symmetrical RAFT agent. It is demonstrated that the amphiphilic statistical outer blocks can provide sufficient stabilization to largely hydrophobic particles in aqueous dispersions. Such a molecular design provides an advantage over copolymers composed only of homoblocks, as a simple variation of the statistical block component ratio provides an efficient way to control the hydrophilicity of the stabilizer block, which ultimately affects the copolymer morphology in solutions and solid films. It was found by small-angle X-ray scattering (SAXS) that the copolymers behaved as dissolved chains in methylethylketone (MEK) but self-assembled in water into stable and well-defined spherical particles that increased in size with the length of the hydrophobic PBA block. These particles possessed an additional particulate surface structure formed by the statistical copolymer stabilizer block, which self-folded through the hydrophobic interactions between the styrene units. SAXS and atomic force microscopy showed that the copolymer films cast from the MEK solutions formed structures predicted by self-consistent field theory for symmetrical triblock copolymers, while the aqueous dispersions formed structural morphologies similar to a close-packed spheres, as would be expected for copolymer particles trapped kinetically due to the restricted movement of the blocks in the initial aqueous dispersion. A strong correlation between the structural morphology and mechanical properties of the films was observed. It was found that the properties of the solvent cast films were highly dependent on the ratios of the hard [poly(AA-st-St)] and soft (PBA) blocks, while the aqueous cast films did not show such a dependence. The continuous phase of hard blocks, always formed in the case of the aqueous cast films, produced films with a higher elastic modulus and a lower extension-to-break in a comparison with the solvent-cast films.

Control of Particle Size in the Self-Assembly of Amphiphilic Statistical Copolymers.

A range of amphiphilic statistical copolymers is synthesized where the hydrophilic component is either methacrylic acid (MAA) or 2-(dimethylamino)ethyl methacrylate (DMAEMA) and the hydrophobic component comprises methyl, ethyl, butyl, hexyl, or 2-ethylhexyl methacrylate, which provide a broad range of partition coefficients (log P). Small-angle X-ray scattering studies confirm that these amphiphilic copolymers self-assemble to form well-defined spherical nanoparticles in an aqueous solution, with more hydrophobic copolymers forming larger nanoparticles. Varying the nature of the alkyl substituent also influenced self-assembly with more hydrophobic comonomers producing larger nanoparticles at a given copolymer composition. A model based on particle surface charge density (PSC model) is used to describe the relationship between copolymer composition and nanoparticle size. This model assumes that the hydrophilic monomer is preferentially located at the particle surface and provides a good fit to all of the experimental data. More specifically, a linear relationship is observed between the surface area fraction covered by the hydrophilic comonomer required to achieve stabilization and the log P value for the hydrophobic comonomer. Contrast variation small-angle neutron scattering is used to study the internal structure of these nanoparticles. This technique indicates partial phase separation within the nanoparticles, with about half of the available hydrophilic comonomer repeat units being located at the surface and hydrophobic comonomer-rich cores. This information enables a refined PSC model to be developed, which indicates the same relationship between the surface area fraction of the hydrophilic comonomer and the log P of the hydrophobic comonomer repeat units for the anionic (MAA) and cationic (DMAEMA) comonomer systems. This study demonstrates how nanoparticle size can be readily controlled and predicted using relatively ill-defined statistical copolymers, making such systems a viable attractive alternative to diblock copolymer nanoparticles for a range of industrial applications.

Advancements in the development on new liquid embolic agents for use in therapeutic embolisation.

Liquid formulations have a well-established role in therapeutic embolisation of blood vessels with the widespread use of cyanoacrylate glues, precipitating polymer suspensions, sclerosing agents and viscous emulsions of oil and chemotherapeutic agents. There is currently an emerging market for next generation liquid embolics which aim to address some of the short-comings of the currently used products. These next generation systems use varying chemistries in their approach to formulate new systems including polymerising, precipitating and phase-transitioning mechanisms to form solidified masses in situ within the vasculature. Some of these emerging technologies have been developed to possess improved imaging properties such as inherent radiopacity, rather than relying on having to mixing with radiopaque materials such as tantalum powder and reduction of X-ray imaging artefacts (streaking). Others offer solvent-free formulations which gel on contact with blood thereby allowing precise control over gel formation during the embolisation process without the use of potentially toxic solvents. In this review, we discuss the role of liquid agents in therapeutic embolisation and the potential of emerging technologies under development for use in the next generation of embolics.

Medium-Chain Fatty Acids Released from Polymeric Electrospun Patches Inhibit Candida albicans Growth and Reduce the Biofilm Viability.

Oral candidiasis is a very common oral condition among susceptible individuals, with the main causative organism being the fungus Candida albicans. Current drug delivery systems to the oral mucosa are often ineffective because of short drug/tissue contact times as well as increased prevalence of drug-resistant Candida strains. We evaluated the potency of saturated fatty acids as antifungal agents and investigated their delivery by novel electrospun mucoadhesive oral patches using agar disk diffusion and biofilm assays. Octanoic (C8) and nonanoic (C9) acids were the most effective at inhibiting C. albicans growth on disk diffusion assays, both in solution or when released from polycaprolactone (PCL) or polyvinylpyrrolidone/RS100 (PVP/RS100) electrospun patches. In contrast, dodecanoic acid (C12) displayed the most potent antifungal activity against pre-existing C. albicans biofilms in solution or when released by PCL or PVP/RS100 patches. Both free and patch-released saturated fatty acids displayed a significant toxicity to wild-type and azole-resistant strains of C. albicans. These data not only provide evidence that certain saturated fatty acids have the potential to be used as antifungal agents but also demonstrate that this therapy could be delivered directly to Candida-infected sites using electrospun mucoadhesive patches, demonstrating a potential new therapeutic approach to treat oral thrush.

Mucoadhesive Electrospun Fibre-Based Technologies for Oral Medicine.

Oral disease greatly affects quality of life, as the mouth is required for a wide range of activities including speech, food and liquid consumption. Treatment of oral disease is greatly limited by the dose forms that are currently available, which suffer from short contact times, poor site specificity, and sensitivity to mechanical stimulation. Mucoadhesive devices prepared using electrospinning offer the potential to address these challenges by allowing unidirectional site-specific drug delivery through intimate contact with the mucosa and with high surface areas to facilitate drug release. This review will discuss the range of electrospun mucoadhesive devices that have recently been reported to address oral inflammatory diseases, pain relief, and infections, as well as new treatments that are likely to be enabled by this technology in the future.

Incorporation of lysozyme into a mucoadhesive electrospun patch for rapid protein delivery to the oral mucosa.

The delivery of biopharmaceuticals to the oral mucosa offers a range of potential applications including antimicrobial peptides to treat resistant infections, growth factors for tissue regeneration, or as an alternative to injections for systemic delivery. Existing formulations targeting this site are typically non-specific and provide little control over dose. To address this, an electrospun dual-layer mucoadhesive patch was investigated for protein delivery to the oral mucosa. Lysozyme was used as a model antimicrobial protein and incorporated into poly(vinylpyrrolidone)/Eudragit RS100 polymer nanofibers using electrospinning from an ethanol/water mixture. The resulting fibrous membranes released the protein at a clinically desirable rate, reaching 90 ± 13% cumulative release after 2 h. Dual fluorescent fibre labelling and confocal microscopy demonstrated the homogeneity of lysozyme and polymer distribution. High encapsulation efficiency and preservation of enzyme activity were achieved (93.4 ± 7.0% and 96.1 ± 3.3% respectively). The released lysozyme inhibited the growth of the oral bacterium Streptococcus ratti, providing further evidence of retention of biological activity and illustrating a potential application for treating and preventing oral infections. An additional protective poly(caprolactone) backing layer was introduced to promote unidirectional delivery, without loss of enzyme activity, and the resulting dual-layer patches displayed long residence times using an in vitro test, showing that the adhesive properties were maintained. This study demonstrates that the drug delivery system has great potential for the delivery of therapeutic proteins to the oral mucosa.

Insights into the internal structures of nanogels using a versatile asymmetric-flow field-flow fractionation method.

Poly(N-isopropylacrylamide) (pNIPAM) nanogels are a highly researched type of colloidal material. In this work, we establish a versatile asymmetric-flow field-flow fractionation (AF4) method that can provide high resolution particle sizing and also structural information on nanogel samples from 65-310 nm in hydrodynamic diameter and so different chemical compositions. To achieve this online multi-angle light scattering and dynamic light scattering detectors were used to provide measurement of the radius of gyration (R g) and hydrodynamic radius (R h) respectively. Two different eluents and a range of cross-flows were evaluated in order to provide effective fractionation and high recovery for the different nanogel samples. We found that using 0.1 M NaNO3 as the eluent and an initial cross-flow of 1 mL min-1 provided optimal separation conditions for all samples tested. Using this method, we analysed two types of samples, pNIPAM nanogels prepared by free radical dispersion polymerisation with increasing diameters and analysed poly(acrylic acid)-b-pNIPAM crosslinked nanogels prepared by reversible addition-fragmentation chain transfer dispersion polymerisation. We could determine that the differently sized free radical nanogels possessed differing internal structures; shape factors (R g/R h) ranged from 0.58-0.73 and revealed that the smallest nanogel had a homogeneous internal crosslinking density, while the larger nanogels had a more densely crosslinked core compared to the shell. The poly(acrylic acid)-b-pNIPAM crosslinked nanogels displayed clear core-shell structures due to all the crosslinking being contained in the core of the nanogel.

Inhibition of ice crystal growth by synthetic glycopolymers: implications for the rational design of antifreeze glycoprotein mimics.

A series of structurally diverse polymers, containing either peptide or vinyl-derived backbones, was tested for ice recrystallization inhibition activity, which is commonly associated with antifreeze (glyco)proteins. It was revealed that only polymers bearing hydroxyl groups in the side chain could inhibit ice growth. Furthermore, well-defined glycopolymers were shown to have a small but significant recrystallization inhibition effect, showing that it may be possible to design antifreeze glycoprotein mimics based upon polymers derived from vinyl monomers.