RGDS-Modified Superporous Poly(2-Hydroxyethyl Methacrylate)-Based Scaffolds as 3D In Vitro Leukemia Model.

Superporous poly(2-hydroxyethyl methacrylate-co-2-aminoethyl methacrylate) (P(HEMA-AEMA)) hydrogel scaffolds are designed for in vitro 3D culturing of leukemic B cells. Hydrogel porosity, which influences cell functions and growth, is introduced by adding ammonium oxalate needle-like crystals in the polymerization mixture. To improve cell vitality, cell-adhesive Arg-Gly-Asp-Ser (RGDS) peptide is immobilized on the N-(γ-maleimidobutyryloxy)succinimide-activated P(HEMA-AEMA) hydrogels via reaction of SH with maleimide groups. This modification is especially suitable for the survival of primary chronic lymphocytic leukemia cells (B-CLLs) in 3D cell culture. No other tested stimuli (interleukin-4, CD40 ligand, or shaking) can further improve B-CLL survival or metabolic activity. Both unmodified and RGDS-modified P(HEMA-AEMA) scaffolds serve as a long-term (70 days) 3D culture platforms for HS-5 and M2-10B4 bone marrow stromal cell lines and MEC-1 and HG-3 B-CLL cell lines, although the adherent cells retain their physiological morphologies, preferably on RGDS-modified hydrogels. Moreover, the porosity of hydrogels allows direct cell lysis, followed by efficient DNA isolation from the 3D-cultured cells. P(HEMA-AEMA)-RGDS thus serves as a suitable 3D in vitro leukemia model that enables molecular and metabolic assays and allows imaging of cell morphology, interactions, and migration by confocal microscopy. Such applications can prospectively assist in testing of drugs to treat this frequently recurring or refractory cancer.

CP MAS kinetics in soft matter: Spin diffusion, local disorder and thermal equilibration in poly(2-hydroxyethyl methacrylate).

The 1H-13C cross-polarization magic angle spinning kinetics was studied in poly(2-hydroxyethyl methacrylate) (pHEMA), i.e. a soft material with high degrees of internal freedom and molecular disorder, having the purpose to track the influence of increasing local incoherent contributions to the effects of coherent nature in the open quantum spin systems. The experimental CP MAS kinetic curves were analyzed in the frame of the models of isotropic and anisotropic spin diffusion with thermal equilibration. The rates of spin diffusion and spin-lattice relaxation as well as the profiles of distribution of dipolar coupling, the parameters accounting the effective size of spin clusters and the local order parameters were determined. The intensities of the peaks of periodic quasi-equilibrium origin gradually decrease with increasing disorder, i.e. going from most ordered to more disordered sites in the polymer. Assuming that the thermal motion induced by the temperature gradients is much faster than the equilibration driven by spin diffusion due the difference in spin temperatures, it was deduced that the thermal equilibration in pHEMA occurs in the time scale of 10-4 s. This is one order of magnitude faster than the spectral spin diffusion, which occurs between spins having different resonance frequencies. The thermal equilibration in the case of remote spin clusters was described by the 'stretched exponent' decay. This led to the fractal dimension Dp ≈ 1.65 for both carbon sites (quaternary and carbonyl). The obtained Dp value corresponds to the aggregates, which images are very similar to those for pHEMA and some other related polymer structures are usually conceived.

Understanding the Structure and Dynamics of Nanocellulose-Based Composites with Neutral and ionic Poly(methacrylate) Derivatives using Inelastic Neutron Scattering and DFT Calculations.

Bacterial nanocellulose (BC)-based composites containing poly(2-hydroxyethyl methacrylate) (PHEMA), poly(methacroylcholine chloride) (PMACC) or poly(methacroylcholine hydroxide) (PMACH) were characterized by inelastic neutron scattering (INS) spectroscopy, combined with DFT (density functional theory) calculations of model systems. A reasonable match between calculated and experimental spectral lines and their intensities was used to support the vibrational assignment of the observed bands and to validate the possible structures. The differences between the spectra of the nanocomposites and the pure precursors indicate that interactions between the components are stronger for the ionic poly(methacrylate) derivatives than for the neutral counterpart. Displaced anions interact differently with cellulose chains, due to the different ability to compete with the O-H···O hydrogen bonds in cellulose. Hence, the INS is an adequate technique to delve deeper into the structure and dynamics of nanocellulose-based composites, confirming that they are true nanocomposite materials instead of simple mixtures of totally independent domains.

Multidose Preservative Free Eyedrops by Selective Removal of Benzalkonium Chloride from Ocular Formulations.

PURPOSE: About 70% of eye drops contain benzalkonium chloride (BAK) to maintain sterility. BAK is an effective preservative but it can cause irritation and toxicity. We propose to mitigate ocular toxicity without compromising sterility by incorporating a filter into an eye drop bottle to selectively remove BAK during the process of drop instillation. METHODS: The filter is a packed bed of particles made from poly(2-hydroxyethyl methacrylate) (pHEMA), which is a common ophthalmic material. We showed that pHEMA particle prepared by using ethoxylated trimethylolpropane triacrylate as crosslinker can be incorporated into a modified eyedrop bottle tip to selectively remove the preservative as the formulation is squeezed out of the bottle. Hydraulic permeability of the plug is measured to determine the resistance to eye drop squeezing, and % removal of BAK and drugs are determined. RESULTS: The modified tip has a hydraulic permeability of about 2 Darcy, which allows eyedrops formulations to flow through without excessive resistance. The tip is designed such that the patients can create an eyedrop of solution of 1-10 cP viscosity in 4 s with a nominal pressure. During this short contact time, the packed particles removed nearly 100% of benzalkonium chloride (BAK) from a 15 mL, 0.012% BAK solution but have only minimal impact on the concentration of contained active components. CONCLUSION: Our novel design can eliminate the preservative induced toxicity from eye drops thereby impacting hundreds of millions of patients with chronic ophthalmic diseases like glaucoma and dry eyes.

Chitosan-functionalised poly(2-hydroxyethyl methacrylate) core-shell microgels as drug delivery carriers: salicylic acid loading and release.

This work presents the evaluation of chitosan-functionalised poly(2-hydroxyethyl methacrylate) (CS/PHEMA) core-shell microgels as drug delivery carriers. CS/PHEMA microgels were prepared by emulsifier-free emulsion polymerisation with N,N '-methylenebisacrylamide (MBA) as a crosslinker. The study on drug loading, using salicylic acid (SA) as a model drug, was performed. The results showed that the encapsulation efficiency (EE) increased as drug-to-microgel ratio was increased. Higher EE can be achieved with the increase in degree of crosslinking, by increasing the amount of MBA from 0.01 g to 0.03 g. In addition, the highest EE (61.1%) was observed at pH 3. The highest release of SA (60%) was noticed at pH 2.4, while the lowest one (49.4%) was obtained at pH 7.4. Moreover, the highest release of SA was enhanced by the presence of 0.2 M NaCl. The pH- and ionic-sensitivity of CS/PHEMA could be useful as a sustained release delivery device, especially for oral delivery.

Sphere formation of adipose stem cell engineered by poly-2-hydroxyethyl methacrylate induces in vitro angiogenesis through fibroblast growth factor 2.

A number of researchers have been reporting a wide range of in vitro and in vivo studies of cell engraftment to enhance angiogenesis using stem cells. Despite these efforts, studies involving three-dimensional (3D) culture method that mimics in vivo environment have not reached its peak yet. In this study, we investigated the change and effects on cellular angiogenic growth factors through sphere formation of adipose stem cell (ASC) which is engineered by poly-2-hydroxyethyl methacrylate (Poly-HEMA). First of all, we successfully induced sphere formation of ASC (sph-ASC) on Poly-HEMA coated plates. sph-ASC represented significantly higher expression levels of anti-apoptotic and hypoxic factors compared to monolayer adherent ASC (adh-ASC). Interestingly, sph-ASC showed higher mRNA levels of the following genes; CD31, CD144, vWF, IGF-2, MCP-1, PDGF-A, VEGF-A, VEGF-C, and FGF-2. In addition, mRNA expressions of angiogenic growth factor receptors such as Flk1, FGFR1, FGFR2, and Tie2 were elevated in sph-ASC. In protein level, Cytokine/Chemokines antibody array revealed a significant increase of FGF-2 in sph-ASC (3.17-fold) compared to adh-ASC. To investigate the effects of FGF-2 on sph-ASC, Matrigel angiogenic invasion assay showed significant reduced level of FGF-2 in FGF-2 siRNA transfected sph-ASC (2.27-fold) compared to negative control siRNA transfected sph-ASC. These findings suggest that Poly-HEMA coated plates induce sphere formation of ASC which has significantly higher expression of FGF-2, and plays a critical role as a major regulating growth factor of in vitro angiogenesis.

Preparation of well-defined poly(2-hydroxyethyl methacrylate) macromonomers via atom transfer radical polymerization.

A series of six near-monodisperse methacrylic macromonomers is prepared via atom transfer radical polymerization (ATRP) of 2-hydroxyethyl methacrylate using a tertiary amine-functionalized initiator at 50 °C, followed by quaternization with excess 4-vinylbenzyl chloride at 20 °C. GPC analyses indicate polydispersities of around 1.20 and their mean degrees of polymerization (DP) range from 20 to 70, as judged by both (1) H NMR and UV spectroscopy. The former technique is more convenient but the latter proved more accurate for the higher DP values, provided that an appropriate model compound is utilized for calibration. Finally, these new macromonomers are used to prepare sterically stabilized polystyrene latexes with relatively narrow size distributions via alcoholic dispersion polymerization.

Loose-fit polypseudorotaxanes constructed from γ-CDs and PHEMA-PPG-PEG-PPG-PHEMA.

A pentablock copolymer was prepared via the atom transfer radical polymerization of 2-hydroxyethyl methacrylate (HEMA) initiated by 2-bromoisobutyryl end-capped PPO-PEO-PPO as a macroinitiator in DMF. Attaching PHEMA blocks altered the self-assembly process of the pentablock copolymer with γ-CDs in aqueous solution. Before attaching the PHEMA, the macroinitiator was preferentially bent to pass through the inner cavity of γ-CDs to give rise to tight-fit double-chain stranded polypseudorotaxanes (PPRs). After attaching the PHEMA, the resulting pentablock copolymer was single-chain stranded into the interior of γ-CDs to form more stable, loose-fit PPRs. The results of (1)H NMR, WXRD, DSC, TGA, (13)C CP/MAS NMR and FTIR analyses indicated that γ-CDs can accommodate and slip over PHEMA blocks to randomly distribute along the entire pentablock copolymer chain. This results in unique, single-chain stranded PPRs showing no characteristic channel-type crystal structure.

Porous Poly(2-hydroxyethyl methacrylate) Hydrogel Scaffolds for Tissue Engineering: Influence of Crosslinking Systems and Silk Sericin Concentration on Scaffold Properties.

Tailored porous structures of poly(2-hydroxyethyl methacrylate) (PHEMA) and silk sericin (SS) were used to create porous hydrogel scaffolds using two distinct crosslinking systems. These structures were designed to closely mimic the porous nature of the native extracellular matrix. Conventional free radical polymerization of 2-hydroxyethyl methacrylate (HEMA) was performed in the presence of different concentrations of SS (1.25, 2.50, 5.00% w/v) with two crosslinking systems. A chemical crosslinking system with N'N-methylene bisacrylamide (MBAAm) and a physical crosslinking system with dimethylurea (DMU) were used: C-PHEMA/SS (crosslinked using MBAAm) and C-PHEMA/pC-SS (crosslinked using MBAAm and DMU). The focus of this study was on investigating the impact of these crosslinking methods on various properties of the scaffolds, including pore size, pore characteristics, polymerization time, morphology, molecular interaction, in vitro degradation, thermal properties, and in vitro cytotoxicity. The various crosslinked networks were found to appreciably influence the properties of the scaffolds, especially the pore sizes, in which smaller sizes and higher numbers of pores with high regularity were seen in C-PHEMA/1.25 pC-SS (17 ± 2 µm) than in C-PHEMA/1.25 SS (34 ± 3 µm). Semi-interpenetrating networks were created by crosslinking PHEMA-MBAAm-PHEMA while incorporating free protein molecules of SS within the networks. The additional crosslinking step involving DMU occurred through hydrogen bonding of the -C=O and -N-H groups with the SS, resulting in the simultaneous incorporation of DMU and SS within the PHEMA networks. As a consequence of this process, the scaffold C-PHEMA/pC-SS exhibited smaller pore sizes compared to scaffolds without DMU crosslinking. Moreover, the incorporation of higher loadings of SS led to even smaller pore sizes. Additionally, the gelation time of C-PHEMA/pC-SS was delayed due to the presence of DMU in the crosslinking system. Both porous hydrogel scaffolds, C-PHEMA/pC-SS and PHEMA, were found to be non-cytotoxic to the normal human skin dermal fibroblast cell line (NHDF cells). This promising result indicates that these hydrogel scaffolds have potential for use in tissue engineering applications.

Synthesis and Evaluation of Antifungal and Antibacterial Abilities of Carbon Nanotubes Grafted to Poly(2-hydroxyethyl methacrylate) Nanocomposites.

Developing nanomaterials with the capacity to restrict the growth of bacteria and fungus is of current interest. In this study, nanocomposites of poly(2-hydroxyethyl methacrylate) (PHEMA) and carbon nanotubes (CNTs) functionalized with primary amine, hydroxyl, and carboxyl groups were prepared and characterized. An analysis by Fourier-transform infrared (FT-IR) spectroscopy showed that PHEMA chains were grafted to the functionalized CNTs. X-ray photoelectron spectroscopy suggested that the grafting reaction was viable. The morphology of the prepared nanocomposites studied by field-emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM) showed significant changes with respect to the observed for pure PHEMA. The thermal behavior of the nanocomposites studied by differential scanning calorimetry (DSC) revealed that the functionalized CNTs strongly affect the mobility of the PHEMA chains. Tests carried out by thermogravimetric analysis (TGA) were used to calculate the degree of grafting of the PHEMA chains. The ability of the prepared nanocomposites to inhibit the growth of the fungus Candida albicans and the bacteria Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli was evaluated. A reduced antifungal and antibacterial capacity of the prepared nanocomposites was determined.

Superhydrophilic Poly(2-hydroxyethyl methacrylate) Hydrogel with Nanosilica Covalent Coating: A Promising Contact Lens Material for Resisting Tear Protein Deposition and Bacterial Adhesion.

Tear protein deposition and bacterial adhesion are the main drawbacks of the hydrogel contact lens. In this study, we developed a novel superhydrophilic poly(2-hydroxyethyl methacrylate) (NSCC-pHEMA) hydrogel with nanosilica covalent coating by the combination of colloidal silica immersion and dehydration treatment. The infrared spectroscopy and energy dispersive X-ray spectroscopy analyses confirmed the successful formation of Si-O covalent bonding between nanosilica and pHEMA hydrogel. This coating was highly stable against powerful sonication or long-term shaking immersion treatment. Among various NSCC-pHEMA hydrogels with different colloidal silica concentrations, the 7%NSCC-pHEMA hydrogel generated a superhydrophilic micro wrinkle surface with a root-mean-square roughness of 43.10 nm, which dramatically reduced the deposition of lysozyme and bovine serum albumin by 65% and 57%, respectively, and decreased the adhesion of S. aureus and E. coli by 59% and 66%, respectively, in comparison to the pHEMA hydrogel. However, the nanosilica coating had little effect on the mechanical properties, light transmittance, oxygen permeability, and equilibrium water content of the pHEMA hydrogel. NSCC-pHEMA hydrogels were nontoxic to both mouse fibroblasts (L929) and human immortalized keratinocytes (HaCaT). Thus, the superhydrophilic NSCC-pHEMA hydrogel is a potential contact lens material for resisting tear protein deposition and bacterial adhesion.

Tailoring the Electron Trapping Effect of a Biocompatible Triboelectric Hydrogel by Graphene Oxide Incorporation towards Self-Powered Medical Electronics.

Triboelectric nanogenerators (TENGs) are associated with several drawbacks that limit their application in the biomedical field, including toxicity, thrombogenicity, and poor performance in the presence of fluids. By proposing the use of a hemo/biocompatible hydrogel, poly(2-hydroxyethyl methacrylate) (pHEMA), this study bypasses these barriers. In contact-separation mode, using polytetrafluoroethylene (PTFE) as a reference, pHEMA generates an output of 100.0 V, under an open circuit, 4.7 µA, and 0.68 W/m2 for an internal resistance of 10 MΩ. Our findings unveil that graphene oxide (GO) can be used to tune pHEMA's triboelectric properties in a concentration-dependent manner. At the lowest measured concentration (0.2% GO), the generated outputs increase to 194.5 V, 5.3 µA, and 1.28 W/m2 due to the observed increase in pHEMA's surface roughness, which expands the contact area. Triboelectric performance starts to decrease as GO concentration increases, plateauing at 11% volumetric, where the output is 51 V, 1.76 µA, and 0.17 W/m2 less than pHEMA's. Increases in internal resistance, from 14 ΩM to greater than 470 ΩM, ζ-potential, from -7.3 to -0.4 mV, and open-circuit characteristic charge decay periods, from 90 to 120 ms, are all observed in conjunction with this phenomenon, which points to GO function as an electron trapping site in pHEMA's matrix. All of the composites can charge a 10 µF capacitor in 200 s, producing a voltage between 0.25 and 3.5 V and allowing the operation of at least 20 LEDs. The triboelectric output was largely steady throughout the 3.33 h durability test. Voltage decreases by 38% due to contact-separation frequency, whereas current increases by 77%. In terms of pressure, it appears to have little effect on voltage but boosts current output by 42%. Finally, pHEMA and pHEMA/GO extracts were cytocompatible toward fibroblasts. According to these results, pHEMA has a significant potential to function as a biomaterial to create bio/hemocompatible TENGs and GO to precisely control its triboelectric outputs.

Poly(2-hydroxyethyl methacrylate-co-quaternary ammonium salt chitosan) hydrogel: A potential contact lens material with tear protein deposition resistance and antimicrobial activity.

Tear protein deposition resistance and antimicrobial property are two challenges of conventional poly(2-hydroxyethyl methacrylate) (pHEMA) contact lenses. In this work, we developed a poly(2-hydroxyethyl methacrylate-co-quaternary ammonium salt chitosan) hydrogel, named as p(HEMA-co-mHACC) hydrogel, using acryloyl HACC (mHACC) as a macromolecular crosslinker. With increasing the acryloyl substitution degree (14-29%) or mHACC content (2-11%), the hydrogel showed an enhanced tensile strength (432-986 kPa) and Young's modulus (360-1158 kPa), a decreased elongation at break (242-84%), and an increased visible light transmittance (0-95%). At an optimal acryloyl substitution degree of 26%, with the increase of mHACC content from 2% to 11%, p(HEMA-co-mHACC) hydrogel presented a decreased water contact angle from 84.6 to 55.3 degree, an increased equilibrium water content from 38% to 45%, and an enhanced oxygen permeability from 8.5 to 13.5 barrer. Due to the enhancement in surface hydrophilicity and electropositivity, p(HEMA-co-mHACC) hydrogel remarkably reduced the deposition of lysozyme, but little affected the adsorption of BSA, depending on the hydrophilic/hydrophobic and electrostatic interactions. The antimicrobial test against Staphylococcus aureus and Escherichia coli showed that p(HEMA-co-mHACC) hydrogel presented an 8-32 times higher germicidal ability than pHEMA hydrogel, indicative of a better antimicrobial activity. The in vitro cell culture of mouse NIH3T3 fibroblasts and immortalized human keratinocytes showed that p(HEMA-co-mHACC) hydrogel was non-toxic. Thus, p(HEMA-co-mHACC) hydrogel with tear protein deposition resistance and antimicrobial activity is a potential candidate for contact lenses.

Determination of ammonium ion using a reagentless amperometric biosensor based on immobilized alanine dehydrogenase.

The use of the enzyme alanine dehydrogenase (AlaDH) for the determination of ammonium ion (NH(4)(+)) usually requires the addition of pyruvate substrate and reduced nicotinamide adenine dinucleotide (NADH) simultaneously to effect the reaction. This addition of reagents is inconvenient when an enzyme biosensor based on AlaDH is used. To resolve the problem, a novel reagentless amperometric biosensor using a stacked methacrylic membrane system coated onto a screen-printed carbon paste electrode (SPE) for NH(4)(+) ion determination is described. A mixture of pyruvate and NADH was immobilized in low molecular weight poly(2-hydroxyethyl methacrylate) (pHEMA) membrane, which was then deposited over a photocured pHEMA membrane (photoHEMA) containing alanine dehydrogenase (AlaDH) enzyme. Due to the enzymatic reaction of AlaDH and the pyruvate substrate, NH(4)(+) was consumed in the process and thus the signal from the electrocatalytic oxidation of NADH at an applied potential of +0.55 V was proportional to the NH(4)(+) ion concentration under optimal conditions. The stacked methacrylate membranes responded rapidly and linearly to changes in NH(4)(+) ion concentrations between 10-100 mM, with a detection limit of 0.18 mM NH(4)(+) ion. The reproducibility of the amperometrical NH(4)(+) biosensor yielded low relative standard deviations between 1.4-4.9%. The stacked membrane biosensor has been successfully applied to the determination of NH(4)(+) ion in spiked river water samples without pretreatment. A good correlation was found between the analytical results for NH(4)(+) obtained from the biosensor and the Nessler spectrophotometric method.

Magnetic Superporous Poly(2-hydroxyethyl methacrylate) Hydrogel Scaffolds for Bone Tissue Engineering.

Magnetic maghemite (γ-Fe2O3) nanoparticles obtained by a coprecipitation of iron chlorides were dispersed in superporous poly(2-hydroxyethyl methacrylate) scaffolds containing continuous pores prepared by the polymerization of 2-hydroxyethyl methacrylate (HEMA) and ethylene dimethacrylate (EDMA) in the presence of ammonium oxalate porogen. The scaffolds were thoroughly characterized by scanning electron microscopy (SEM), vibrating sample magnetometry, FTIR spectroscopy, and mechanical testing in terms of chemical composition, magnetization, and mechanical properties. While the SEM microscopy confirmed that the hydrogels contained communicating pores with a length of ≤2 mm and thickness of ≤400 µm, the SEM/EDX microanalysis documented the presence of γ-Fe2O3 nanoparticles in the polymer matrix. The saturation magnetization of the magnetic hydrogel reached 2.04 Am2/kg, which corresponded to 3.7 wt.% of maghemite in the scaffold; the shape of the hysteresis loop and coercivity parameters suggested the superparamagnetic nature of the hydrogel. The highest toughness and compressive modulus were observed with γ-Fe2O3-loaded PHEMA hydrogels. Finally, the cell seeding experiments with the human SAOS-2 cell line showed a rather mediocre cell colonization on the PHEMA-based hydrogel scaffolds; however, the incorporation of γ-Fe2O3 nanoparticles into the hydrogel improved the cell adhesion significantly. This could make this composite a promising material for bone tissue engineering.

Thiolated poly(2-hydroxyethyl methacrylate) hydrogels as a degradable biocompatible scaffold for tissue engineering.

Research of degradable hydrogel polymeric materials exhibiting high water content and mechanical properties resembling tissues is crucial not only in drug delivery systems but also in tissue engineering, medical devices, and biomedical-healthcare sensors. Therefore, we newly offer development of hydrogels based on poly(2-hydroxyethyl methacrylate-co-2-(acetylthio) ethyl methacrylate-co-2-methacryloyloxyethyl phosphorylcholine) [P(HEMA-ATEMA-MPC)] and optimization of their mechanical and in vitro and in vivo degradability. P(HEMA-ATEMA-MPC) hydrogels differed in chemical composition, degree of crosslinking, and starting molar mass of polymers (15, 19, and 30 kDa). Polymer precursors were synthesized by a reversible addition fragmentation chain transfer (RAFT) polymerization using 2-(acetylthio)ethyl methacrylate containing protected thiol groups, which enabled crosslinking and gel formation. Elastic modulus of hydrogels increased with the degree of crosslinking (Slaughter et al., 2009) [1]. In vitro and in vivo controlled degradation was confirmed using glutathione and subcutaneous implantation of hydrogels in rats, respectively. We proved that the hydrogels with higher degree of crosslinking retarded the degradation. Also, albumin, γ-globulin, and fibrinogen adsorption on P(HEMA-ATEMA-MPC) hydrogel surface was tested, to simulate adsorption in living organism. Rat mesenchymal stromal cell adhesion on hydrogels was improved by the presence of RGDS peptide and laminin on the hydrogels. We found that rat mesenchymal stromal cells proliferated better on laminin-coated hydrogels than on RGDS-modified ones.

Comparative study on water structures of poly(tetrahydrofurfuryl acrylate) and poly(2-hydroxyethyl methacrylate) by nuclear magnetic resonance spectroscopy.

It is well known that poly(2-methoxyethyl acrylate) (PMEA) has good blood compatibility and its performance is attributed to its water structure. Recently, we applied solution nuclear magnetic resonance spectroscopy (solution-NMR) for analyzing the water structure in PMEA at ambient temperature and concluded that this method is useful because of the clear observation of the resonance peaks at low and high magnetic field (downfield and upfield, respectively) areas indicating the existence of more than two types of water. The present study was performed to compare the water structure of poly(tetrahydrofurfuryl acrylate) (PTHFA) and poly(2-hydroxyethyl methacrylate) (PHEMA) using solution 2H-NMR and deuterium oxide as water at the temperature range 15-45 °C. It was found that PTHFA has a different water structure from that of PHEMA. Water in PTHFA clearly showed two resonance peaks at downfield and upfield areas, with different spin-lattice relaxation times, T12H (high and low values, respectively). These observations are similar to those of PMEA. In contrast, PHEMA showed only one broad resonance peak (at downfield) with a low T12H value. Based on these observations, this study discusses the effect of water structures on the blood compatibility of these polymers.

Recombinant human Erythropoietin enhanced the cytotoxic effects of tamoxifen toward the spheroid MCF-7 breast cancer cells.

Erythropoietin (EPO) is widely used to treat anemia in patients undergoing chemotherapy for cancers. The main objective of this study was to investigate the effect of rHuEPO on the response of spheroid breast cancer, MCF-7, cells to tamoxifen treatment. The MCF-7 spheroids were treated with 10 mg/mL tamoxifen in combination with either 0, 10, 100 or 200 IU/mL rHuEPO for 24, 48 or 72 h. The viability of the MCF-7 cells was determined using the annexin-V, cell cycle, caspases activation and acridine orange/propidium iodide staining. rHuEPO-tamoxifen combination significantly (p greater than 0.05) increased the number of spheroid MCF-7 cells entering early apoptotic phase after 12 h and late apoptotic phase after 24 h of treatment; primarily the result of the antiproliferative effect tamoxifen. Tamoxifen alone significantly (p < 0.05) increased the caspase-3 and -9 activities in the spheroid MCF-7 cells by 200 to 550% of the control. Combination rHuEPO and tamoxifen produced much lesser effect on the caspase-8 activity. The rHuEPO in the combination treatment had concentration-dependently caused decrease in the caspase activities. rHuEPO-tamoxifen combination markedly increased MCF-7 cells entering the SubG0/G1 phase of the cell cycle by more than 500% of the control, while decreasing those entering the G2 + M and S phases by 50%. After 72 h, the combination treatment produced greater (p < 0.05) change in the SubG0/G1 phase than tamoxifen treatment alone. Morphologically, spheroid MCF-7 cells subjected to combination rHuEPO-tamoxifen treatment showed nuclear condensation and margination, cytoplasmic blebbing, necrosis, and early and late apoptosis. Thus, the study showed that rHuEPO-tamoxifen combination induced apoptosis in the spheroid MCF-7 cells. The apoptotic effect of the rHuEPO-tamoxifen combination treatment on the MCF-7 cells was greater than that produced by tamoxifen alone. The rHuEPO-tamoxifen treatment enhanced the caspase-independent apoptotic effects of tamoxifen on the spheroid MCF-7 cells.

Synthesis of Poly(2-Hydroxyethyl Methacrylate) (PHEMA)-Based Superparamagnetic Nanoparticles for Biomedical and Pharmaceutical Applications.

The performance of polymeric nanomaterials relies greatly upon their properties which are intimately related to the methods of fabrication of their materials. Among various synthetic polymers the polymers of 2-hydroxyethyl methacrylate (PHEMA) maintains a prime position in the biomedical field due to their useful physicochemical properties and suitability for controlled drug delivery applications. Furthermore, the addition of iron oxide to PHEMA nanoparticles imparts superparamagnetism to the nanoparticles and expands the range of their uses to include magnetic drug targeting applications. Here we focus on three methods for preparation of PHEMA nanoparticles, one by suspension polymerization, a second by emulsion polymerization without the use of any surfactants, and the final one with the incorporation of iron oxide into PHEMA nanoparticles.

Doxorubicin Imprinted Photoluminescent Polymer as a pH-Responsive Nanocarrier.

In this work, an innovative doxorubicin (DOX) imprinted photoluminescent polymer via the precipitation free-radical polymerization strategy was developed based on graphene quantum dots as a pH-responsive nanocarrier. The prepared materials were characterized by Fourier transform infrared, scanning electron microscopy, photoluminescence, and dynamic light scattering techniques. Binding kinetics of DOX established specific recognition binding sites in the photoluminescent nanoscale molecularly imprinted polymer (PLMIP) structure. In vitro drug release behaviors exhibited a pH-controlled release in a sustained manner for the prepared photoluminescent nanocarriers. Due to the presence of pseudopeptide skeletons in the nanocarrier and a positively charged structure, the cytotoxicity study indicated that a DOX-loaded nanocarrier against human lung adenocarcinoma A549 cell lines has notable cytotoxicity. According to the obtained results, the prepared pH-responsive PLMIP has the potential to be employed as an anticancer and biodetection platform.