Graft Modification of Starch Nanoparticles Using Nitroxide-Mediated Polymerization and the "Grafting to" Approach.

Starch nanoparticles (SNP) were modified with synthetic polymers using the "grafting to" approach and nitroxide-mediated polymerization. SG1-capped poly(methyl methacrylate-co-styrene) (P(MMA-co-S)) copolymers with low dispersity and high degree of livingness were first synthesized in bulk. These macroalkoxyamines were then grafted to vinyl benzyl-functionalized SNP to obtain biosynthetic hybrids. The grafted materials, SNP-g-P(MMA-co-S), were characterized by 1H NMR, FTIR, TGA, and elemental analysis. The total amount of grafted polymer and the grafting efficiency were evaluated for different molecular weights (5870-12150 g·mol-1) of the grafted polymer, the polymer addition approach (batch or semibatch) and the initial polymer loading (2.5, 5, or 10 g polymer/g SNP). The proposed approach presented in this work to graft modify SNP allows for a precise surface modification of the nanoparticles, while permitting that the final properties of the resulting biohybrid to be tunable according to the choice of polymer grafted.

Grafting from Starch Nanoparticles with Synthetic Polymers via Nitroxide-Mediated Polymerization.

Nitroxide-mediated polymerization (NMP) is employed to graft synthetic polymers from polysaccharides. This work demonstrates the first successful polymer grafting from starch nanoparticles (SNPs) via NMP. To graft synthetic polymers from the SNPs' surface, the SNPs are first functionalized with 4-vinylbenzyl chloride prior to reaction with BlocBuilder MA yielding a macroinitiator. Methyl methacrylate with styrene, acrylic acid, or methyl acrylate are then grafted from the SNPs. The polymerizations exhibited linear reaction kinetics, indicating that they are well controlled. Thermal gravimetric analysis and spectroscopic techniques confirmed the synthesis of the precursors materials and the success of the grafting from polymerizations. The incorporation of hydrophobic synthetic polymers on hydrophilic SNPs yields new hybrid materials that could find use in several industrial applications including paper coatings, adhesives, and paints.

Poly(oligoethylene glycol methacrylate) dip-coating: turning cellulose paper into a protein-repellent platform for biosensors.

The passivation of nonspecific protein adsorption to paper is a major barrier to the use of paper as a platform for microfluidic bioassays. Herein we describe a simple, scalable protocol based on adsorption and cross-linking of poly(oligoethylene glycol methacrylate) (POEGMA) derivatives that reduces nonspecific adsorption of a range of proteins to filter paper by at least 1 order of magnitude without significantly changing the fiber morphology or paper macroporosity. A lateral-flow test strip coated with POEGMA facilitates effective protein transport while also confining the colorimetric reporting signal for easier detection, giving improved performance relative to bovine serum albumin (BSA)-blocked paper. Enzyme-linked immunosorbent assays based on POEGMA-coated paper also achieve lower blank values, higher sensitivities, and lower detection limits relative to ones based on paper blocked with BSA or skim milk. We anticipate that POEGMA-coated paper can function as a platform for the design of portable, disposable, and low-cost paper-based biosensors.

Designing injectable, covalently cross-linked hydrogels for biomedical applications.

Hydrogels that can form spontaneously via covalent bond formation upon injection in vivo have recently attracted significant attention for their potential to address a variety of biomedical challenges. This review discusses the design rules for the effective engineering of such materials, and the major chemistries used to form injectable, in situ gelling hydrogels in the context of these design guidelines are outlined (with examples). Directions for future research in the area are addressed, noting the outstanding challenges associated with the use of this class of hydrogels in vivo.

Injectable On-Demand Pulsatile Drug Delivery Hydrogels Using Alternating Magnetic Field-Triggered Polymer Glass Transitions.

Remote-controlled pulsatile or staged release has significant potential in a wide range of therapeutic treatments. However, most current approaches are hindered by the low resolution between the on- and off-states of drug release and the need for surgical implantation of larger controlled-release devices. Herein, we describe a method that addresses these limitations by combining injectable hydrogels, superparamagnetic iron oxide nanoparticles (SPIONs) that heat when exposed to an alternating magnetic field (AMF), and polymeric nanoparticles with a glass transition temperature (Tg) just above physiological temperature. Miniemulsion polymerization was used to fabricate poly(methyl methacrylate-co-butyl methacrylate) (p(MMA-co-BMA)) nanoparticles loaded with a model hydrophobic drug and tuned to have a Tg value just above physiological temperature (∼43 °C). Co-encapsulation of these drug-loaded nanoparticles with SPIONs inside a carbohydrate-based injectable hydrogel matrix (formed by rapid hydrazone cross-linking chemistry) enables injection and immobilization of the nanoparticles at the target site. Temperature cycling facilitated a 2.5:1 to 6:1 on/off rhodamine release ratio when the nanocomposites were switched between 37 and 45 °C; release was similarly enhanced by exposing the nanocomposite hydrogel to an AMF to drive heating, with enhanced release upon pulsing observed even 1 week after injection. Coupled with the apparent cytocompatibility of all of the nanocomposite components, these injectable nanocomposite hydrogels are promising as minimally invasive but remotely actuated release delivery vehicles capable of complex release kinetics with high on-off resolution.

A new method for the preparation of concentrated translucent polymer nanolatexes from emulsion polymerization.

A novel method for the preparation of concentrated, colloidally stable, translucent polymer nanolatexes is presented. Herein nanolatexes are obtained from emulsion polymerization, utilizing the potential of catalytic chain transfer to enhance the particle nucleation efficiency. Low amounts of emulsifier are required (<8% w/w based on monomer) while the nanolatexes concentration can be increased to 40% w/w. The nanolatexes are translucent in appearance, which was correlated to the average particle size and width of the particle size distribution using Mie theory. Increasing the nanolatex concentration was found to have no deteriorating effect on either the optical or colloidal properties. Preparing translucent nanolatexes via this method is advantageous, as the amount of emulsifier is significantly reduced without sacrificing the optical transparency or the high interfacial surface area of the polymer colloids.

In situ-gelling starch nanoparticle (SNP)/O-carboxymethyl chitosan (CMCh) nanoparticle network hydrogels for the intranasal delivery of an antipsychotic peptide.

Existing oral or injectable antipsychotic drug delivery strategies typically demonstrate low bioavailability to targeted brain regions, incentivizing the development of alternative delivery strategies. Delivery via the nasal cavity circumvents multiple barriers for reaching the brain but requires drug delivery vehicles with very specific properties to be effective. Herein, we report in situ-gelling and degradable bulk nanoparticle network hydrogels consisting of oxidized starch nanoparticles (SNPs) and carboxymethyl chitosan (CMCh) that enable intranasal delivery via spray, high nasal mucosal retention, and functional controlled release of the peptide drug PAOPA, a positive allosteric modulator of dopamine D2 receptor. PAOPA-loaded SNP-CMCh hydrogels can alleviate negative symptoms like behavioural abnormalities associated with schizophrenia (i.e. decreased social interaction time) for up to 72 h in an MK-801-induced pre-clinical rat model of schizophrenia at a low drug dosage (0.5 mg/kg); in comparison, conventional PAOPA administration via the intraperitoneal route requires twice the PAOPA dose to achieve a therapeutic effect that persists for only a few hours. This strategy offers potential for substantially decreasing re-administration frequencies and overall drug doses (and thus side-effects) of a range of potential antipsychotic drugs via a minimally-invasive administration route.

Graft modification of starch nanoparticles using nitroxide-mediated polymerization and the grafting from approach.

Starch nanoparticles (SNP) are attracting increased attention as a renewable bio-based alternative to petroleum-based polymers in the materials community. In this work, we describe the grafting from of SNP with synthetic polymers via nitroxide-mediated polymerization (NMP). Varying amounts of poly(methyl methacrylate-co-styrene) (P(MMA-co-S)), poly(methyl acrylate) (PMA) and poly(acrylic acid) (PAA) were grafted from the surface of SNP in a three-step process. The grafting of synthetic polymers from the surface of SNP was confirmed by FTIR, 1H NMR, elemental analysis and thermogravimetric analysis. These new tailor-made starch-based hybrid materials could find use in paper coatings, adhesives, paints, as well as in polymer latex applications.

Photopolymerized Starchstarch Nanoparticle (SNP) network hydrogels.

Starch is an attractive biomaterial given its low cost and high protein repellency, but its use in forming functional hydrogels is limited by its high viscosity and crystallinity. Herein, we demonstrate the use of fully amorphous starch nanoparticles (SNPs) as functional hydrogel building blocks that overcome these challenges. Methacrylation of SNPs enables hydrogel formation via photopolymerization, with the low viscosity of SNPs enabling facile preparation of pre-gel suspensions of up to 35 wt% SNPs relative to <10 wt% with linear starch. Small angle neutron scattering indicates a significantly different microstructure in SNP-based hydrogels compared to linear starch-based hydrogels due to the balance between inter- and intra-particle crosslinks, consistent with SNPs forming denser and stiffer hydrogels. Functionalized SNPs are highly cytocompatible at degree of substitution values <0.25 and, once gelled, can effectively repel cell adhesion. The physicochemical versatility and biological functionality of SNP-based hydrogels offer potential in various applications.

Injectable and Degradable Poly(Oligoethylene glycol methacrylate) Hydrogels with Tunable Charge Densities as Adhesive Peptide-Free Cell Scaffolds.

Injectable, dual-responsive, and degradable poly(oligo ethylene glycol methacrylate) (POEGMA) hydrogels are demonstrated to offer potential for cell delivery. Charged groups were incorporated into hydrazide and aldehyde-functionalized thermoresponsive POEGMA gel precursor polymers via the copolymerization of N,N'-dimethylaminoethyl methacrylate (DMAEMA) or acrylic acid (AA) to create dual-temperature/pH-responsive in situ gelling hydrogels that can be injected via narrow gauge needles. The incorporation of charge significantly broadens the swelling, degradation, and rheological profiles achievable with injectable POEGMA hydrogels without significantly increasing nonspecific protein adsorption or chronic inflammatory responses following in vivo subcutaneous injection. However, significantly different cell responses are observed upon charge incorporation, with charged gels significantly improving 3T3 mouse fibroblast cell adhesion in 2D and successfully delivering viable and proliferating ARPE-19 human retinal epithelial cells via an "all-synthetic" matrix that does not require the incorporation of cell-adhesive peptides.

Carbohydrate functionalized hybrid latex particles.

In this review we highlight the progress in the synthesis of carbohydrate functionalized hybrid latex particles, focusing on different synthetic approaches which use carbohydrates as a surfactant/stabilizer, initiator, grafting site and/or as a macromonomer. These nanocomposites are receiving increasing attention in academia as well as in industry, due to increasingly stringent societal demands for biobased, biodegradable, and biocompatible materials. Furthermore, we will report on the use of nanostructured carbohydrate materials, such as cellulose nanocrystals, starch nanocrystals, and starch nanoparticles. These novel materials represent an interesting emerging field, and examples of latex nanocomposites have only recently been reported. It is the authors' opinion that using carbohydrate materials for the synthesis and production of latex polymers will become of increasing importance as we move towards a more sustainable future.

A Highly Sensitive Immunosorbent Assay Based on Biotinylated Graphene Oxide and the Quartz Crystal Microbalance.

A high-sensitivity flow-based immunoassay is reported based on a gold-coated quartz crystal microbalance (QCM) chip functionalized directly in the QCM without requiring covalent conjugation steps. Specifically, the irreversible adsorption of a biotinylated graphene oxide-avidin complex followed by loading of a biotinylated capture antibody is applied to avoid more complex conventional surface modification chemistries and enable chip functionalization and sensing all within the QCM instrument. The resulting immunosensors exhibit significantly lower nonspecific protein adsorption and stronger signal for antigen sensing relative to simple avidin-coated sensors. Reproducible quantification of rabbit IgG concentrations ranging from 0.1 ng/mL to 10 µg/mL (6 orders of magnitude) can be achieved depending on the approach used to quantify the binding with simple mass changes used to detect higher concentrations and a horseradish peroxidase-linked detection antibody that converts its substrate to a measurable precipitate used to detect very low analyte concentrations. Sensor fabrication and assay performance take ∼5 h in total, which is on par with or faster than other techniques. Quantitative sensing is possible in the presence of complex protein mixtures, such as human plasma. Given the broad availability of biotinylated capture antibodies, this method offers both an easy and flexible platform for the quantitative sensing of a variety of biomolecule targets.

Injectable Interpenetrating Network Hydrogels via Kinetically Orthogonal Reactive Mixing of Functionalized Polymeric Precursors.

The enhanced mechanics, unique chemistries, and potential for domain formation in interpenetrating network (IPN) hydrogels have attracted significant interest in the context of biomedical applications. However, conventional IPNs are not directly injectable in a biological context, limiting their potential utility in such applications. Herein, we report a fully injectable and thermoresponsive interpenetrating polymer network formed by simultaneous reactive mixing of hydrazone cross-linked poly(N-isopropylacrylamide) (PNIPAM), and thiosuccinimide cross-linked poly(N-vinylpyrrolidone) (PVP). The resulting IPN gels rapidly (<1 min) after injection without the need for heat, UV irradiation, or small-molecule cross-linkers. The IPNs, cross-linked by kinetically orthogonal mechanisms, showed a significant synergistic enhancement in shear storage modulus compared to the individual component networks as well as distinctive pore morphology, degradation kinetics, and thermal swelling; in particular, significantly lower hysteresis was observed over the thermal phase transition relative to single-network PNIPAM hydrogels.

Injectable and tunable poly(ethylene glycol) analogue hydrogels based on poly(oligoethylene glycol methacrylate).

Injectable PEG-analogue hydrogels based on poly(oligoethylene glycol methacrylate) have been developed based on complementary hydrazide and aldehyde reactive linear polymer precursors. These hydrogels display the desired biological properties of PEG, form covalent networks in situ following injection, and are easily modulated for improved control over their functionality and physiochemical properties.

Injectable poly(oligoethylene glycol methacrylate)-based hydrogels with tunable phase transition behaviours: physicochemical and biological responses.

The potential of poly(oligoethylene glycol methacrylate) (POEGMA) hydrogels with varying thermosensitivities as soft materials for biomedical applications is demonstrated. Hydrogels are prepared from hydrazide and aldehyde functionalized POEGMA precursors, yielding POEGMA hydrogels with a volume phase transition temperature (VPTT) below (PO0), close to (PO10) and well above (PO100) physiological temperature. Hydrogels with VPTTs close to and above physiological temperature exhibit biological properties similar to those typically observed for poly(ethylene glycol) hydrogels (i.e. low protein adsorption, low cell adhesion and minimal inflammatory responses in vivo) while hydrogels with VPTTs lower than physiological temperature exhibit biological properties more analogous to poly(N-isopropylacrylamide) above its phase transition temperature (temperature-switchable cell adhesion, higher protein adsorption and somewhat more acute inflammation in vivo). As such, the use of POEGMA precursors with varying chain lengths of ethylene oxide grafts offers a versatile platform for the design of hydrogels with tunable physiological properties via simple copolymerization.

The synthesis of translucent polymer nanolatexes via microemulsion polymerization.

The potential of an extremely hydrophobic cobalt(II) catalyst for the synthesis of polymer nanolatexes in microemulsion polymerization is investigated. Colloidally stable nanolatexes have been successfully synthesized in microemulsion polymerization of styrene, butyl methacrylate, and 2-ethylhexyl methacrylate and in the presence of bis[(difluoronoryl)-diphenylglyoximato]cobalt(II). The average particle diameter can be reduced from 50 nm to approximately 10 nm in the presence of minor quantities of the cobalt(II) complex. The small particle size, combined with the relatively narrow particle size distribution, results in nanolatexes that are virtually transparent in appearance. Furthermore, the nucleation efficiency can be enhanced by up to two orders of magnitude, corresponding to approximately 1 particle nucleated for every 10(1) micelles. This represents a significant improvement as in microemulsion polymerization generally 1 particle is nucleated for every 10(3) micelles.

Determination of the Critical Chain Length of Oligomers in Dispersion Polymerization.

The critical chain length (jcrit) in dispersion polymerization is systematically investigated utilizing low molecular weight poly(methyl methacrylate) oligomers synthesized by catalytic chain transfer polymerization. The solubility of these oligomers in methanol/water media of different compositions and at different temperatures has been visually determined. The results show that the solubility of the oligomers increases with increasing methanol fraction and increasing temperature. The constructed solubility map allows for an estimate of jcrit as a function of these important polymerization parameters. Furthermore, it is found that the value of jcrit changes with the concentration of the oligomers in the methanol/water medium, an important consideration for understanding the nucleation stage of a dispersion polymerization. The obtained results have been successfully correlated to earlier data reported on the dispersion polymerization of methyl methacrylate.