Poly(ethylene glycol) methacrylate hydrolyzable microspheres for transient vascular embolization

Poly(ethylene glycol) methacrylate (PEGMA) hydrolyzable microspheres intended for biomedical applications were readily prepared from poly(lactide-co-glycolide) (PLGA)–poly(ethylene glycol) (PEG)–PLGA crosslinker and PEGMA as a monomer using a suspension polymerization process. Additional co-monomers, methacrylic acid and 2-methylene-1,3-dioxepane (MDO), were incorporated into the initial formulation to improve the properties of the microspheres. All synthesized microspheres were spherical in shape, calibrated in the 300–500 μm range, swelled in phosphate-buffered saline (PBS) and easily injectable through a microcatheter. Hydrolytic degradation experiments performed in PBS at 37 °C showed that all of the formulations tested were totally degraded in less than 2 days. The resulting degradation products were a mixture of low-molecular-weight compounds (PEG, lactic and glycolic acids) and water-soluble polymethacrylate chains having molecular weights below the threshold for renal filtration of 50 kg mol⁻¹ for the microspheres containing MDO. Both the microspheres and the degradation products were determined to exhibit minimal cytotoxicity against L929 fibroblasts. Additionally, in vivo implantation in a subcutaneous rabbit model supported the in vitro results of a rapid degradation rate of microspheres and provided only a mild and transient inflammatory reaction comparable to that of the control group.     

Preparation of poly(methyl methacrylate) microspheres modified with amino acid moieties

Poly(methyl methacrylate) microspheres [poly(SerMA-co-MMA), poly(AlaMAm-co-MMA), poly(AlaEMA-co-MMA), and poly(AlaMAm/AlaEMA-co-MMA)] modified with O-methacryloyl-L -serine (SerMA), N-methacryloyl-L -alanine (AlaMAm) and L -alanine 2-methacryloyloxyethyl ester (AlaEMA) were prepared by the emulsifier-free emulsion copolymerization of methyl methacrylate (MMA) with SerMA, AlaMAm and AlaEMA, respectively, initiated with 2,2′-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (ABIP). The series of polymer microspheres showed unimodal distribution of the particle size (290–800 nm) in water. From X-ray photoelectron spectroscopy it was concluded that the amino acid moieties are located on the surface of the particles in all cases. Poly(SerMA-co-MMA) showed the most effective suppression of adsorption of proteins such as albumin (Alb), γ-globulin (Glo) and fibrinogen (Fib) among the examined poly(methylmethacrylate) microspheres.     

Poly(methyl methacrylate) containing pyrrole moieties in the side chains

Two synthetic routes to copolymers 7 of methyl methacrylate (MMA) with 2-(N-pyrrolyl)ethyl methacrylate (PEMA, 11 ) are compared. Copolymerization of MMA (4) with 2-bromoethyl methacrylate (BEMA, 3 ) leads to a precursor copolymer 5 . The reactivity ratios are close to unity (r_MMA = 0,90, r_BEMA = 0,92). The polymer-analogous reaction of 5 with N-pyrrolylpotassium (6) runs to 99% conversion of the BEMA units. The synthesis of PEMA (11) is presented. The reactivity ratios of copolymerization of this monomer (11) with MMA (4) are determined to r_MMA = 1.05 and r_PEMA = 1,65. Copolymers 7 are further characterized by ¹H nuclear magnetic resonance, infrared spectroscopy, gel-permeation chromatography and differential scanning calorimetry.     

Poly (acrylic acid) chitosan interpolymer complexes for stomach controlled antibiotic delivery

The aim of this study was to develop a stomach-specific drug delivery system to increase the efficacy of amoxicillin against Helicobacter pylori. Polyacrylic acid (PAA), chitosan (CS), and amoxicillin (A) were employed to obtain polyionic complexes. The design of the hydrogel delivery system was based on the swellable approach; with a floating feature to prolong the Gastric Residence Time (GRT). The polyionic complex (PAA:CS:A 2.5:5:2) showed a sustained drug release profile in enzyme-free simulated gastric fluid (SGF) and pH 4.0. A pH independent swelling-eroding pattern with adequate maximum swelling ratios of 17.76 and 13.42 was obtained at in SGF and pH 4.0, respectively, with similar eroding profiles in both pH media. This network carrier provides an amoxicillin protective effect towards the hydrolytic degradation in SGF. The in vivo study was performed on healthy volunteers, using the [13C] octanoic acid breath test. The proposed hydrogel showed a prolonged GRT of up to 3 h. The preliminary results from this study suggest that amoxicillin polyionic complexes have potential for improving local antibiotic therapy against H. pylori.     

Phase Separation in Poly(9,9‐dioctylfluorene)/Poly(methyl methacrylate) Blends

Binary blends of the conjugated polymer poly(9,9‐dioctylfluorene) (PFO) and the insulating polymer poly(methyl methacrylate) (PMMA) phase‐separated and exhibited optical and electrical activity in light‐emitting‐diodes. The phase‐separated PFO columns were uniformly packed and situated directly on a transparent hole‐injecting contact. The length scales of lateral topographical features can be adjusted discretionarily by controlling the blend concentration and compositional ratio. The mechanism leading to the formation of lateral structures was investigated by comparing with the vertical segregation in polar conjugated polymer poly(9,9‐bis(6‐diethoxylphosphorylhexyl)fluorene) (PF‐EP) blends with PMMA, which suggested that kinetics rather than interfacial free energy acted. In such lateral phase‐separated structures, the phase‐separated PFO domains were the optically and electrically active phase. This highlighted the potential opportunity as nanoscale light source for organic optoelectronic device applications with well‐controllable properties.

     

Enthalpy Relaxation in Poly(4‐hydroxystyrene)/Poly(methyl methacrylate) Blends

Summary: The influence of blend composition on enthalpy relaxation behaviour was assessed for miscible blends of poly(4‐hydroxystyrene)/poly(methyl methacrylate) (PHS/PMMA). Values of enthalpy lost (ΔH(T_a, t_a)) were calculated from experimental data plotted against log₁₀(t_a) and modelled using the Cowie‐Ferguson (CF) semi‐empirical model. This gives a set of values for three adjustable parameters, ΔH_∞(T_a), log₁₀(t_c) and β. The blends relaxed more slowly than PMMA, but more quickly and less co‐operatively than PHS. Moreover, the blends released more enthalpy than PMMA, but less than PHS. The enthalpy lost by the fully relaxed glass (ΔH_∞(T_a)) was less than the theoretical amount possible on reaching the state defined by the liquid enthalpy line extrapolated into the glassy region (ΔH_max(T_a)). Infrared spectroscopy was used for assessing the hydrogen bonding interactions in the blends. The ageing results are discussed with reference to the hydrogen bonding interactions.

Dependence of ΔT (□) and ΔC_p (?) on PHS/PMMA blend composition.     

Synthesis of Cyclic Poly(methyl methacrylate) Directly from Dihalogenated Linear Precursors

Cyclic poly(methyl methacrylate) (PMMA) is prepared by intramolecular radical trap‐assisted atom transfer radical coupling (RTA‐ATRC) of dihalogenated PMMA precursors. The inclusion of the radical trap nitrosobenzene (NBz) in the coupling sequence affords high yields of cyclic polymers, as observed by gel permeation chromatography and confirmed by ¹H NMR and electrospray ionization mass spectra, which show the presence of the aromatic group from the NBz incorporated into the cycle. Analogous coupling reactions in the absence of the radical trap do not lead to appreciable cyclization or even intermolecular elongation, consistent with chain‐end sterics preventing radical–radical coupling as the predominant termination pathway. Thermolysis of the cyclic PMMA, possible because of the labile C? O bond in the alkoxyamine linkage contained in the macrocycle, causes a reversion back to the linear form and is consistent with the role of the radical trap in the coupling sequence. Differential scanning calorimetry is also used to compare cyclic PMMA with its linear analog, with a marked increase in glass transition temperatures found after cyclization.

     

Degradation of Poly(methyl methacrylate) Model Compounds Under Extreme Environmental Conditions

There is a significant knowledge gap in the degradation of poly(methyl methacrylate) (pMMA) under conditions experienced by surface coatings in the harsh Australian environment. In the current study pMMA model compounds were exposed to 95 °C temperatures and high UV radiation (1 kW · m^?2), separately as well as in combination. Contrary to the findings of previous studies, degradation proceeds in these conditions via a non‐radical cyclic mechanism. The mechanism was further confirmed by synthesis and degradation of ethylene‐oxide‐terminated pMMA, an intermediate product in the cycle. Electrospray ionisation mass spectrometry analysis of thermally degraded samples after 155 weeks shows degradation consistent with the proposed cycle in vinyl‐terminated pMMA, while saturated pMMA was shown to be stable after the same period. Saturation delayed the UV‐induced degradation, yet these compounds still displayed some slight degradation after 52 weeks, confirming the terminal vinyl bond in pMMA as a weak point. Combined UV and thermal radiation after 56 weeks showed degradation of both pMMA samples, with the vinyl‐terminated sample also exhibiting crosslinking. The combination of thermal and UV radiation also caused acceleration of degradation, shown by a comparison of the polymer samples after ≈60 weeks.

     

Melt-Versus Solution-Extrusion Additive Manufacturing of Poly(methyl methacrylate) Medical Implant Prototypes

The development of tailored additive manufacturing (AM) approaches is resulting in novel strategies for engineering the macro/microstructural details of potential medical devices made of biocompatible polymers. The aim of this work is the employment of a multifunctional AM machine for fabricating poly(methyl methacrylate) (PMMA) constructs with a predefined shape and porous architecture, by either melt- or solution-extrusion AM. In particular, PMMA porous scaffolds are manufactured by employing fused filament fabrication (FFF) or computer-aided wet-spinning (CAWS). The comparative characterization of the two developed PMMA implant prototypes demonstrates significant differences in terms of porous structure, polymer surface topography, material composition, glass transition temperature, and mechanical properties. As a consequence, FFF-printed PMMA samples support a faster in vitro proliferation of a murine fibroblast cell line in comparison to PMMA scaffolds by CAWS. The results achieved encourage further research on the developed processing protocols, aimed at the development of tailored PMMA implants for personalized surgery applications.     

Nano‐Level Mixing of ZnO into Poly(methyl methacrylate)

A simple, facile and versatile approach is presented for the preparation of PMMA/ZnO nanocomposite materials, which possess high transparency, no color, good thermal stability, UV absorption and improved mechanical properties. The employed process involved mixing of ZnO nanoparticles dispersed in DMAc with the PMMA matrix dissolved in the same solvent. The effect of ZnO content on the physical properties of the PMMA matrix is studied. A significant improvement in mechanical properties was observed with the incorporation of 0.5 wt.‐% ZnO particles. The beauty of the described approach lies in the fact that despite being a simple and facile approach, it offers nano‐level (2–5 nm) mixing of ZnO nanoparticles into a polymer matrix.

     

New Complex Crystals of Chiral Poly(L‐lactic acid) and Different Tactic Poly(methyl methacrylate)

Based on evidence from differential scanning calorimetry (DSC), wide‐angle X‐ray diffraction (WAXD), and Fourier‐transform infrared (FTIR) spectroscopy, a new stereocomplex crystal (DSC T_m = 175 °C, with WAXD 2θ = 10.0° and 12.5°) is proven for the first time between structurally dissimilar chiral poly(L ‐lactic acid) (PLLA) and syndiotactic poly(methyl methacrylate) (sPMMA). There is a strong complexing capacity only between low molecular weight PLLA and sPMMA, in miscible state, at specific weight fractions (70:30). The complexing capacity is more significant when the mixtures are melt‐crystallized at T_c = 110 °C or lower, and the intensity of this complex can be further enhanced if it is annealed between 100 and 160 °C, below its T_m = 175 °C. The new complex crystal can be formed only between PLLA and sPMMA, but not with isotactic or atactic PMMA.     

Graphene Oxide–Poly(ethylene glycol) methyl ether methacrylate Nanocomposite Hydrogels

In this paper, covalently linked graphene oxide–poly(ethylene glycol) methyl ether methacrylate–reversible addition‐fragmentation chain transfer (GO–PEGMEMA–RAFT) and physically mixed GO–PEGMEMA hydrogel nanocomposites are synthesized. Spectroscopic and imaging techniques such as UV–vis, Fourier transform infrared, Raman spectroscopy, and transmission electron microscopy show that the PEGMEMA is successfully grafted on GO sheets. The rheology of the nanocomposites is studied by small angle oscillatory shear, which shows a competition between reinforcement and lubrication behavior of GO. In the case where lubrication effect dominates reinforcement, the covalently linked GO–PEGMEMA–RAFT has higher G′ compared to the physically mixed GO‐PEGMEMA. Hence, in the covalently linked system, the grafted polymer chains appear to minimize the lubrication effect.

     

The Aggregation Behavior of Poly(ethylene oxide)‐Poly(methyl methacrylate) Diblock Copolymers in Organic Solvents

Poly(ethylene oxide)‐poly(methyl methacrylate) and poly(ethylene oxide)‐poly(deuteromethyl methacrylate) block copolymers have been prepared by group transfer polymerization of methyl methacrylate (MMA) and deuteromethyl methacrylate (MMA‐d₈), respectively, using macroinitiators containing poly(ethylene oxide) (PEO). Static and dynamic light scattering and surface tension measurements were used to study the aggregation behavior of PEO‐PMMA diblock copolymers in the solvents tetrahydrofuran (THF), acetone, chloroform, N,N‐dimethylformamide (DMF), 1,4‐dioxane and 2,2,2‐trifluoroethanol. The polymer chains are monomolecularly dissolved in 1,4‐dioxane, but in the other solvents, they form large aggregates. Solutions of partially deuterated and undeuterated PEO‐PMMA block copolymers in THF have been studied by small‐angle neutron scattering (SANS). Generally, large structures were found, which cannot be considered as micelles, but rather fluctuating structures. However, ¹H NMR measurements have shown that the block copolymers form polymolecular micelles in THF solution, but only when large amounts of water are present. The micelles consist of a PMMA core and a PEO shell.     

Preparation and characterization of photoresponsive poly(methyl methacrylate) microspheres bearing phosphorylcholine-analogous and spirooxazine moieties

The photoresponsive copolymer microspheres [poly(MAIP-co-MMA)] were prepared from the emulsifier-free emulsion copolymerization of 2-[2-(methacryloyloxy) ethyldimethylammonio]-ethyl indolinonaphthooxazine phosphate (MAIP) and methyl methacrylate (MMA). From the kinetics of the copolymerization of MAIP and MMA, it was found that the initial rate of polymerization of MMA increased by the addition of a small amount of MAIP. From the X-ray photoelectron spectroscopy (XPS) measurements MAIP moiety was found to be located on the surface of a particle. The introduction of a MAIP moiety into poly(MMA) microspheres results in a decrease in the amount of bovine serum albumin (BSA) adsorbed. A photoresponsive adsorption of BSA on poly(MAIP-co-MMA) microspheres was observed with spirooxazine-merocyanine photoisomerization caused by UV irradiation.     

Poly(methyl methacrylate)-supported isoxazolinium permanganates: preparation and application as oxidising reagents

Divinylbenzene (DVB), ethylene glycol dimethacrylate (EGDMA) and N,N′-methylenebis(acrylamide) (N,N′MBA) crosslinked poly(methyl methacrylate) (PMMA) was functionalised to generate isoxazolinium permanganate resins. These resins were found to selectively oxidise alcohols to the corresponding carbonyl compounds in appreciable yields. These reagents were found to possess the characteristics of polymeric reagents including operational simplicity.     

Poly(lactic-co-glycolic acid) electrospun fibrous meshes for the controlled release of retinoic acid

Poly(lactic-co-glycolic acid) (PLGA) meshes loaded with retinoic acid (RA) were prepared by applying the electrospinning technique. The purpose of the present work was to combine the biological effects of RA and the advantages of electrospun meshes to enhancing the mass transfer features of controlled release systems and cell interaction with polymeric scaffolds. The processing conditions for the fabrication of three-dimensional meshes were optimized by studying their influence on mesh morphology. Tensile testing showed that RA loading influenced the meshes’ mechanical properties by increasing their strength and rigidity. Moreover, the drug release and degradation profiles of the electrospun systems were compared to analogous RA-loaded PLGA films prepared by solvent casting. The results of this study highlight that the electrospun meshes preserved their fibrous structure after 4 months under in vitro physiological conditions and showed a sustained controlled release of the loaded agent in comparison to that observed for cast films. The bioactivity of the loaded RA was investigated on murine preosteoblasts cells by evaluating its influence on cell proliferation and morphology.     

Poly(acrylic acid)-grafted Poly(N-isopropyl acrylamide) Networks: Preparation,Characterization and Hydrogel Behavior

Poly(acrylic acid)-grafted poly(N-isopropylacrylamide) co-polymer networks (PNIPAAm-g-PAA) were prepared via the reversible addition-fragmentation transfer (RAFT) polymerization of N-isopropyl- acrylamide (NIPAAm) with trithiocarbonate-terminated PAA as a macromolecular chain-transfer agent in the presence of N,N-methylenebisacrylamide. The PNIPAAm-g-PAA co-polymer networks were characterized by means of Fourier transform infrared spectroscopy, differential scanning calorimetry and small-angle X-ray scattering. It is found that the PNIPAAm-g-PAA co-polymer networks were microphase-separated, in which the microdomains of PNIPAAm-PAA interpolymer complexes were dispersed into the PNIPAAm matrix. The PNIPAAm-g-PAA hydrogels displayed a dual response to temperature and pH values. The thermoresponsive properties of PNIPAAm-g-PAA networks were investigated. Below the volume phase transition temperatures, the PNIPAAm-g-PAA hydrogels possessed much higher swelling ratios than control PNIPAAm hydrogel. In terms of swelling, deswelling and reswelling tests, it is judged that the PNIPAAm-g-PAA hydrogels displayed faster response to the external temperature changes than control PNIPAAm hydrogel. The improved thermoresponsive properties of hydrogels are ascribed to the formation of PAA-grafted PNIPAAm networks, in which the water-soluble PAA chains behave as the hydrophiphilic tunnels and allow water molecules to go through and, thus, to accelerate the diffusion of water molecules.     

Poly(methyl methacrylate)-block-poly(ethyl acrylate) by group transfer polymerization: synthesis and structural characterization

Poly(methyl methacrylate)-block-poly(ethyl acrylate) (PMMA-block-PEA) was synthesized by sequential group transfer polymerization (GTP) in tetrahydrofuran at ?30°C using (1-methoxy-2-methyl-1-propenyloxy)trimethylsilane (MTS) as an initiator and tetrabutylammonium fluoride monohydrate (TBAF · H₂O) as a catalyst. First, the PMMA macroinitiator was prepared in situ in quantitative conversion and its lifetime was at least 15 min. In the second step, an equimolar amount of ethyl acrylate was polymerized with a conversion of 67–88% and PMMA-block-PEA with number-average molecular weight 5000 < M?_n < 11 500 and polydispersity 1,4 < M?_w/M?_n < 2,1 was obtained. The number of chains almost does not change during the polymerization and the initiating efficiency of MTS was in both steps ca. 0,65–0,80. The diblock structure of the copolymer was confirmed by the ¹³C NMR spectrometric direct proof of the bond-linking of both blocks and by comparing the DSC behaviour of the copolymer with that of the corresponding blend of the homopolymers. No contamination of the block copolymer with the homopolymers was detected by the analytical methods used for the structural characterizations.     

Viscosity-molecular weight relationships for low molecular weight polymers. II. Poly(vinyl acetate) and poly(methyl methacrylate)

[η]/M?_n relationships at 25°C. have been found for low molecular weight fractions of poly(vinyl acetate) (PV Ac) in chlorobenzene and poly(methyl methacrylate) (PMMA) in toluene. The PMMA used contains about 75% of syndiotactic form. Due to the difficulties of PMMA fractionation, the constants in the equation [η] = K M? refer to an average degree of polydispersity equal to M?_w/M?_n = 1.2. For both PVAc and PMMA there is a range of molecular weight where a = 0.5; in these ranges [η] is practically indistinguishable from [η]Θ.